oxytocin and Body-Weight

Obesity and its associated complications have reached epidemic proportions in the USA and also worldwide, highlighting the need for new and more effective treatments. Although the neuropeptide oxytocin (OXT) is well recognised for its peripheral effects on reproductive behaviour, the release of OXT from somatodendrites and axonal terminals within the central nervous system (CNS) is also implicated in the control of energy balance. In this review, we summarise historical data highlighting the effects of exogenous OXT as a short-term regulator of food intake in a context-specific manner and the receptor populations that may mediate these effects. We also describe what is known about the physiological role of endogenous OXT in the control of energy balance and whether serum and brain levels of OXT relate to obesity on a consistent basis across animal models and humans with obesity. We describe recent data on the effectiveness of chronic CNS administration of OXT to decrease food intake and weight gain or to elicit weight loss in diet-induced obese (DIO) and genetically obese mice and rats. Of clinical importance is the finding that chronic central and peripheral OXT treatments both evoke weight loss in obese animal models with impaired leptin signalling at doses that are not associated with visceral illness, tachyphylaxis or adverse cardiovascular effects. Moreover, these results have been largely recapitulated following chronic s.c. or intranasal treatment in DIO non-human primates (rhesus monkeys) and obese humans, respectively. We also identify plausible mechanisms that contribute to the effects of OXT on body weight and glucose homeostasis in rodents, non-human primates and humans. We conclude by describing the ongoing challenges that remain before OXT-based therapeutics can be used as a long-term strategy to treat obesity in humans.

Topics: Animals; Appetitive Behavior; Blood Glucose; Body Weight; Homeostasis; Humans; Oxytocin

The neurohypophysial endocrine system is identified here as a potential target for therapeutic interventions toward improving obesity-related metabolic dysfunction, given its coinciding pleiotropic effects on psychological, neurological and metabolic systems that are disrupted in obesity.. Copeptin, the C-terminal portion of the precursor of arginine-vasopressin, is positively associated with body mass index and risk of type 2 diabetes. Plasma oxytocin is decreased in obesity and several other conditions of abnormal glucose homeostasis. Recent data also show non-classical tissues, such as myocytes, hepatocytes and β-cells, exhibit responses to oxytocin and vasopressin receptor binding that may contribute to alterations in metabolic function. The modulation of anorexigenic and orexigenic pathways appears to be the dominant mechanism underlying the effects of oxytocin and vasopressin on body weight regulation; however, there are apparent limitations associated with their use in direct pharmacological applications. A clearer picture of their wider physiological effects is needed before either system can be considered for therapeutic use.

Topics: Animals; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Eating; Energy Metabolism; Gastrointestinal Microbiome; Glucose; Hepatocytes; Homeostasis; Humans; Insulin Resistance; Lipid Metabolism; Muscle Cells; Obesity; Oxytocin; Vasopressins

The neurohormone oxytocin (OXT) impacts food intake as well as cognitive, emotional, and social functioning-all of which are central to eating disorder (ED) pathology across the weight spectrum. Here, we review findings on endogenous OXT levels and their relationship to ED pathology, the impact of exogenous OXT on mechanisms that drive ED presentation and chronicity, and the potential role of genetic predispositions in the OXT-ED link.. Current findings suggest a role of the OXT system in the pathophysiology of anorexia nervosa. In individuals with bulimia nervosa, endogenous OXT levels were comparable to those of healthy controls, and exogenous OXT reduced food intake. Studies in other ED are lacking. However, genetic studies suggest a broad role of the OXT system in influencing ED pathology. Highlighting findings on why OXT represents a potential biomarker of and treatment target for ED, we advocate for a systematic research approach spanning the entire ED spectrum.

Topics: Anorexia Nervosa; Body Weight; Bulimia Nervosa; Feeding and Eating Disorders; Humans; Neuropeptides; Oxytocin

The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus. The physiological functions of oxytocin and vasopressin depend on their secretion, which is principally determined by the pattern of action potentials initiated at the cell bodies. Appropriate secretion of oxytocin and vasopressin to meet the challenges of changing physiological conditions relies mainly on integration of afferent information on reproductive, osmotic, and cardiovascular status with local regulation of magnocellular neurons by glia as well as intrinsic regulation by the magnocellular neurons themselves. This review focuses on the control of magnocellular neuron activity with a particular emphasis on their regulation by reproductive function, body fluid balance, and cardiovascular status. © 2016 American Physiological Society. Compr Physiol 6:1701-1741, 2016.

Topics: Animals; Body Weight; Brain; Humans; Morphine Dependence; Neurons; Osmosis; Oxytocin; Peptides

The basic mechanisms that lead obesity are not fully understood; however, several peptides undoubtedly play a role in regulating body weight. Obesity, a highly complex metabolic disorder, involves central mechanisms that control food intake and energy expenditure. Previous studies have shown that central or peripheral oxytocin administration induces anorexia. Recently, in an apparent discrepancy, rodents that were deficient in oxytocin or the oxytocin receptor were shown to develop late-onset obesity without changing their total food intake, which indicates the physiological importance of oxytocin to body metabolism. Oxytocin is synthesized not only within magnocellular and parvocellular neurons but also in several organs, including the ovary, uterus, placenta, testis, thymus, kidney, heart, blood vessels, and skin. The presence of oxytocin receptors in neurons, the myometrium and myoepithelial cells is well recognized; however, this receptor has also been identified in other tissues, including the pancreas and adipose tissue. The oxytocin receptor is a typical class I G protein-coupled receptor that is primarily linked to phospholipase C-β via Gq proteins but can also be coupled to other G proteins, leading to different functional effects. In this review, we summarize the present knowledge of the effects of oxytocin on controlling energy metabolism, focusing primarily on the role of oxytocin on appetite regulation, thermoregulation, and metabolic homeostasis.

Topics: Adipose Tissue; Appetite Regulation; Body Temperature Regulation; Body Weight; Eating; Energy Metabolism; Homeostasis; Humans; Leptin; Neurons; Obesity; Oxytocin; Phospholipase C beta; Receptors, Oxytocin

Obesity and its associated metabolic disorders are growing health concerns in the US and worldwide. In the US alone, more than two-thirds of the adult population is classified as either overweight or obese [1], highlighting the need to develop new, effective treatments for these conditions. Whereas the hormone oxytocin is well known for its peripheral effects on uterine contraction during parturition and milk ejection during lactation, release of oxytocin from somatodendrites and axonal terminals within the central nervous system (CNS) is implicated in both the formation of prosocial behaviors and in the control of energy balance. Recent findings demonstrate that chronic administration of oxytocin reduces food intake and body weight in diet-induced obese (DIO) and genetically obese rodents with impaired or defective leptin signaling. Importantly, chronic systemic administration of oxytocin out to 6 weeks recapitulates the effects of central administration on body weight loss in DIO rodents at doses that do not result in the development of tolerance. Furthermore, these effects are coupled with induction of Fos (a marker of neuronal activation) in hindbrain areas (e.g. dorsal vagal complex (DVC)) linked to the control of meal size and forebrain areas (e.g. hypothalamus, amygdala) linked to the regulation of food intake and body weight. This review assesses the potential central and peripheral targets by which oxytocin may inhibit body weight gain, its regulation by anorexigenic and orexigenic signals, and its potential use as a therapy that can circumvent leptin resistance and reverse the behavioral and metabolic abnormalities associated with DIO and genetically obese models.

Topics: Adult; Animals; Appetite Depressants; Appetite Regulation; Body Weight; Energy Metabolism; Humans; Oxytocin; Signal Transduction; Weight Loss

The intent of this paper is to evaluate decreases of food intake and body weight that occur when a peptide is administered to an animal. Using the pancreatic hormone insulin as an example, the case is made that endogenous insulin is normally secreted in response to circulating nutrients as well as in proportion to the degree of adiposity. Hence, its levels in the blood are a reliable indicator of adiposity. A further case is then made demonstrating that insulin is transported through the blood-brain barrier into the brain, where it gains access to neurons containing specific insulin receptors that are important in the control of feeding and metabolism. Finally, experimentally-induced changes of insulin in the brain cause predictable changes of food intake and body weight. Given these observations, the question is then asked: since endogenous insulin, acting within the brain, appears to decrease food intake, can a decrease of food intake caused by exogenous insulin administered into the same area of the brain be ascribed to the same, naturally-occurring response system, or should it be attributed to malaise or a non-specific depression of behavior? Arguments are presented supporting the former position that exogenous insulin, when administered in small quantities directly into the brain, taps into the natural caloric/metabolic system and hence influences food intake and body weight.

Topics: Animals; Body Weight; Brain; Eating; Insulin; Oxytocin; Rats

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Animals; Blood Vessels; Body Weight; Catecholamines; Cats; Dogs; Electric Stimulation; Guinea Pigs; Haplorhini; Histamine; Humans; Mice; Muscle Contraction; Muscle, Smooth; Organ Size; Oxytocin; Parasympathetic Nervous System; Parasympathomimetics; Prostaglandins; Rabbits; Rats; Regional Blood Flow; Serotonin; Spleen; Sympathetic Nervous System; Vasopressins

The aim of this study was to evaluate the effect of body weight, oxytocin deposition in the uterus at artificial insemination (AI), vaginal cytology, serum progesterone (P

Topics: Animals; Body Fluids; Body Weight; Breeding; Dogs; Female; Fertility; Infertility; Insemination, Artificial; Litter Size; Male; Oxytocin; Pregnancy; Risk Factors; Semen; Treatment Outcome; Vagina

Neonatal isolation results in long-lasting negative alterations to the brain and behavior. Some of these changes include effects on non-spatial learning and memory, sociability and neuroendocrine levels. Theoretically, neonatal tactile stimulation should reverse the impacts of neonatal isolation; however, this remains unknown for changes relating to learning, memory, sociability and hormones in social animals. Using socially monogamous mandarin voles (Microtus mandarinus), the long-lasting effects of these early manipulations on anxiety-like behavior, novel object recognition, sociability, and neuroendocrine levels were investigated. Compared with neonatal-isolated males, males subjected to the same manipulation but accompanied with tactile stimulation had heavier body weights across PND4-18 and displayed significantly less anxiety-like behavior in an open field test. In addition, tactile stimulation increased the preference index for novel object recognition reduced by neonatal isolation. Compared with control males, neonatal-isolated males engaged in less body contact with unfamiliar same-sex individuals and this effect was reversed by neonatal tactile stimulation. Tactile stimulation enhanced aggressive behavior in neonatal-isolated males and increased the levels of AVP and OT in the paraventricular nucleus (PVN) which were decreased by neonatal isolation. This early manipulation also reduced serum CORT levels that were significantly up-regulated by neonatal isolation in both neonatal and adult offspring. These results indicate that adequate tactile stimulation in early life plays an important role in the prevention of behavioral disturbances induced by neonatal isolation, possibly through the alteration of central OT, AVP and the serum corticosterone levels.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Arginine Vasopressin; Arvicolinae; Body Weight; Corticosterone; Exploratory Behavior; Female; Interpersonal Relations; Male; Neuroendocrine Cells; Oxytocin; Paraventricular Hypothalamic Nucleus; Physical Stimulation; Recognition, Psychology; Social Isolation; Stress, Psychological; Touch

Although the primary cause of exercise-associated hyponatremia (EAH) is relative overconsumption of fluids beyond the kidneys' ability to excrete excess fluid, the mechanisms limiting maximum renal excretory ability during exercise remain to be elucidated.. The objective of the study was to: 1) perform a comprehensive evaluation of the endocrine secretion of pituitary, natriuretic and adrenal steroid hormones, and cytokines immediately before and after running an ultramarathon; and 2) evaluate the relationship between osmotic and nonosmotic stimuli to arginine vasopressin (AVP) secretion within the overall context of assessing the hormonal regulation of fluid balance during prolonged endurance exercise.. This was an observational study.. The study setting was a 56-km ultramarathon.. Eighty-two runners participated in the study.. There were no interventions.. Plasma sodium concentration [Na(+)] and plasma volume [(AVP)(p)] were measured.. Fluid homeostasis during exercise (356 +/- 4 min) was maintained with ad libitum fluid intakes. [Na(+)] was maintained from before the race (139.3 +/- 0.3 mmol/liter) to after the race (138.1 +/- 0.4 mmol/liter) with a significant decrease in plasma volume (-8.5 +/- 0.1%, P < 0.01). Increases in the plasma (AVP)(p) (3.9-fold), oxytocin (1.9-fold), brain natriuretic peptide (4.5-fold), and IL-6 (12.5-fold) were highly significant (P < 0.0001). Changes in brain natriuretic peptide, oxytocin, and corticosterone were associated with 47% of the variance noted in (AVP)(p) and 13% of the variance in plasma [Na(+)] in pathway analyses.. (AVP)(p) was markedly elevated after the ultramarathon despite unchanged plasma [Na(+)](.) Therefore, an inability to maximally suppress (AVP)(P) during exercise as a result of nonosmotic stimulation of AVP secretion may contribute to the pathogenesis of exercise-associated hyponatremia if voluntary fluid intake were to exceed fluid output.

Topics: Arginine Vasopressin; Body Weight; Exercise; Female; Hormones; Humans; Hyponatremia; Male; Models, Biological; Osmosis; Oxytocin; Physical Endurance; Time Factors; Water-Electrolyte Balance

In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.

Topics: Adult; Blood Pressure; Body Height; Body Weight; Carboprost; Cesarean Section; Dinoprost; Disease Susceptibility; Drug Combinations; Ergonovine; Female; Gastrointestinal Diseases; Humans; Nausea; Oxytocin; Parity; Postpartum Hemorrhage; Pregnancy; Random Allocation; Single-Blind Method; Tromethamine

Topics: Age Factors; Body Weight; Bradycardia; Cesarean Section; Clinical Trials as Topic; Delivery, Obstetric; Diarrhea; Female; Fetal Diseases; Humans; Infant, Newborn; Labor, Induced; Muscle Tonus; Nausea; Oxytocin; Parity; Phlebitis; Pregnancy; Prostaglandins; Vomiting

Topics: Apgar Score; Body Weight; Bradycardia; Cervix Uteri; Cesarean Section; Clinical Trials as Topic; Diarrhea; Evaluation Studies as Topic; Female; Fetal Heart; Humans; Infant, Newborn; Labor, Induced; Nausea; Obstetric Labor Complications; Oxytocin; Parity; Pregnancy; Prostaglandins; Vomiting

Topics: Body Weight; Clinical Trials as Topic; Female; Gestational Age; Humans; Infant Mortality; Infant, Newborn; Labor, Induced; Methods; Muscle Contraction; Oxytocin; Parity; Pregnancy; Pregnancy Complications; Pregnancy, Prolonged; Prostaglandins; Time Factors

Topics: Adolescent; Adult; Apgar Score; Birth Weight; Body Weight; Clinical Trials as Topic; Delivery, Obstetric; Evaluation Studies as Topic; Female; Humans; Labor, Induced; Oxytocin; Parity; Pregnancy; Prostaglandins; Stimulation, Chemical; Time Factors; Uterus

Weighted blankets have emerged as a potential non-pharmacological intervention to ease conditions such as insomnia and anxiety. Despite a lack of experimental evidence, these alleged effects are frequently attributed to a reduced activity of the endogenous stress systems and an increased release of hormones such as oxytocin and melatonin. Thus, the aim of the present in-laboratory crossover study (26 young and healthy participants, including 15 men and 11 women) was to investigate if using a weighted blanket (~12% of body weight) at bedtime resulted in higher salivary concentrations of melatonin and oxytocin compared with a light blanket (~2.4% of body weight). We also examined possible differences in salivary concentrations of the stress hormone cortisol, salivary alpha-amylase activity (as an indicative metric of sympathetic nervous system activity), subjective sleepiness, and sleep duration. When using a weighted blanket, the 1 hour increase of salivary melatonin from baseline (i.e., 22:00) to lights off (i.e., 23:00) was about 32% higher (p = 0.011). No other significant differences were found between the blanket conditions, including subjective sleepiness and total sleep duration. Our study is the first to suggest that using a weighted blanket may result in a more significant release of melatonin at bedtime. Future studies should investigate whether the stimulatory effect on melatonin secretion is observed on a nightly basis when frequently using a weighted blanket over weeks to months. It remains to be determined whether the observed increase in melatonin may be therapeutically relevant for the previously described effects of the weighted blanket on insomnia and anxiety.

Topics: Adult; Body Weight; Circadian Rhythm; Cross-Over Studies; Female; Humans; Male; Melatonin; Oxytocin; Sleep; Sleep Initiation and Maintenance Disorders; Sleepiness

Sex steroid hormones are important for the maintenance of metabolism in both sexes. Oxytocin (OT) is a neuropeptide that is synthesized in hypothalamic regions, secreted from the posterior lobe of the pituitary gland, and is involved in the control of appetite, body weight, and metabolism. Estrogen and OT both play a role in the metabolism of nutrients, and OT has potential in the prevention of obesity. However, the relationship between testosterone and OT remains unclear. Therefore, the present study investigated the relationship between testosterone and OT in hypogonadal male rats and male rats receiving testosterone replacement therapy. The results obtained showed that testosterone increased serum OT levels and promoted the secretion of adiponectin from visceral fat, and reduced body fat directly and/or indirectly through OT and adiponectin. Testosterone also increased the expression of OT receptors in the hypothalamus to increase sensitivity to OT, and perhaps because of this, OT administration had the effect of reducing food intake and body weight gain in both normal and castrated rats, and this effect was stronger in normal rats. In other words, the preventative effects of OT on obesity may be synergistic with testosterone. Collectively, the present results indicate that testosterone exerts indirect effects to prevent obesity and atherosclerosis through OT and adiponectin. In conclusion, testosterone replacement therapy is useful for preventing obesity caused by hypogonadism, and OT has potential in supportive medicine to prevent obesity and adult diseases.

Topics: Adiponectin; Animals; Body Weight; Female; Male; Obesity; Oxytocin; Rats; Testosterone

Evidence from animal experiments has shown that the hypothalamic paraventricular nucleus (PVN) plays a key role in regulating body weight and blood glucose levels. However, it is unclear whether neuron populations in the human PVN are involved in the development of type 2 diabetes mellitus (T2DM). To address this, we investigated the neuronal and glial populations in the PVN of 26 T2DM patients and 20 matched controls. Our findings revealed a significant reduction in oxytocin (Oxt) neuron density in the PVN of T2DM patients compared to controls, while other neuronal populations remained unchanged. This suggests that Oxt neurons may play a specific role in the pathophysiology of T2DM. Interestingly, the reduction in Oxt neurons was accompanied by a decreased melanocortinergic input in to the PVN as reflected by a reduction in alpha-MSH immunoreactivity. We also analysed two glial cell populations, as they are important for maintaining a healthy neural microenvironment. We found that microglial density, phagocytic capacity, and their proximity to neurons were not altered in T2DM patients, indicating that the loss of Oxt neurons is independent of changes in microglial immunity. However, we did observe a reduction in the number of astrocytes, which are crucial for providing trophic support to local neurons. Moreover, a specific subpopulation of astrocytes characterized by aquaporin 4 expression was overrepresented in T2DM patients. Since this subset of astrocytes is linked to the glymphatic system, their overrepresentation might point to alterations in the hypothalamic waste clearance system in T2DM. Our study shows selective loss of Oxt neurons in the PVN of T2DM individuals in association with astrocytic reduction and gliovascular remodelling. Therefore, hypothalamic Oxt neurons may represent a potential target for T2DM treatment modalities.

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus

Obesity affects more than a third adult population in the United States; the prevalence is even higher in patients with major depression disorders. GWAS studies identify the receptor tyrosine kinase ErbB4 as a risk gene for obesity and for major depression disorders. We found that ErbB4 was enriched in the paraventricular nucleus of the hypothalamus (PVH). To investigate its role in metabolism, we deleted ErbB4 by injecting a Cre-expressing virus into the PVH of ErbB4-floxed male mice and found that PVH ErbB4 deletion increased weight gain without altering food intake. ErbB4 PVH deletion also reduced nighttime activity and decreased intrascapular brown adipose tissue (iBAT) thermogenesis. Analysis of covariance (ANCOVA) revealed that ErbB4 PVH deletion reduced O

Topics: Adult; Animals; Body Weight; Energy Metabolism; Homeostasis; Humans; Male; Mice; Obesity; Oxytocin; Paraventricular Hypothalamic Nucleus; Receptor, ErbB-4

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.

Topics: Animals; Body Weight; Eating; Female; Humans; Mammals; Obesity; Oxytocin; Polycystic Ovary Syndrome; Rats; Weight Gain

Oxytocin (OXT) is produced in the hypothalamic nuclei and secreted into systemic circulation from the posterior pituitary gland. In the central nervous system, OXT regulates behaviours including maternal and feeding behaviours. Our aim is to evaluate whether oestrogen regulates hypothalamic OXT dynamics. Herein, we provide the first evidence that OXT dynamics in the hypothalamus vary with sex and that oestrogen may modulate dynamic changes in OXT levels, using OXT-mRFP1 transgenic rats. The fluorescence intensity of OXT-mRFP1 and expression of the OXT and mRFP1 genes in the hypothalamic nuclei is highest during the oestrus stage in female rats and decreased significantly in ovariectomised rats. Oestrogen replacement caused significant increases in fluorescence intensity and gene expression in a dose-related manner. This is also demonstrated in the rats' feeding behaviour and hypothalamic Fos neurons using cholecystokinin-8 and immunohistochemistry. Hypothalamic OXT expression is oestrogen-dependent and can be enhanced centrally by the administration of oestrogen.

Topics: Animals; Body Weight; Estrogens; Female; Hypothalamus; Oxytocin; Rats; Rats, Transgenic; Rats, Wistar

Topics: Animals; Body Weight; Eating; Energy Intake; Obesity; Oxytocin; Rats; Rats, Sprague-Dawley

Decades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (Oxt) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation of appetite. Oxt has an anorexigenic effect, as shown in human studies, and can mediate satiety signals in rodents. However, the function of Oxt signaling in the physiological regulation of appetite has remained in question, because whole-body knockout (KO) of

Topics: Animals; Body Weight; Humans; Hyperphagia; Hypothalamus; Hypothalamus, Posterior; Leptin; Mice; Obesity; Oxytocin; Paraventricular Hypothalamic Nucleus; Triglycerides

Recent studies have revealed that the administration of oxytocin has beneficial effects on the regulation of body weight, food intake, and metabolic functions, especially in obese individuals. Obesity is common in women after the menopause and drives many components of metabolic syndrome. Weight gain in menopausal women has been frequently reported. Although obesity and associated metabolic disorders are frequently observed in peri- and postmenopausal women, there are few medical interventions for these conditions. In this study, we evaluated the effects of chronic oxytocin administration on appetite, body weight, and fat mass in peri- and postmenopausal female rats. Sixteen naturally premenopausal or menopausal rats were intraperitoneally injected with oxytocin (1,000 μg/day) for 12 days. The daily changes in their body weight and food intake were measured at the same time as the oxytocin and vehicle injections. Intraperitoneally administering oxytocin for 12 days significantly reduced food intake, body weight, and visceral adipocyte size. In addition, oxytocin administration caused reductions in serum triglyceride and low-density lipoprotein-cholesterol levels, while it did not disturb hepatic or renal functions or locomotor activity. This is the first study to show the effects of oxytocin on the metabolic and feeding functions of peri- and postmenopausal female rats. Oxytocin might be a useful treatment for metabolic disorders caused by the menopause or aging.

Topics: Adipocytes; Aging; Animals; Biomarkers; Body Weight; Climacteric; Eating; Female; Oxytocin; Rats; Rats, Wistar; Sexual Maturation; Weight Gain

In a recent case report involving a male with hypothalamic obesity, concurrent administration of oxytocin (OT) and an opioid receptor antagonist, naltrexone (NTX), synergistically affected energy balance. Here, by using laboratory rats, we examined whether the reported synergy between OT and NTX in the context of food intake extends beyond that one unique case. We found that intravenous OT+NTX combination, at doses subthreshold for each of the drugs individually, decreased episodic consumption of a 10% sucrose solution in non-deprived animals. Daily administration of OT and NTX just before a scheduled, 2-hour, high-fat high-sugar (HFHS) meal over 24 days, decreased cumulative HFHS diet intake, but without a change in body weight due to compensatory standard chow intake during the remainder of the day. The NTX-OT treatment affected expression of several feeding-related genes in the hypothalamus, brain stem and nucleus accumbens, brain regions essential for the regulation of energy- and reward-driven consumption. We conclude that OT and NTX act synergistically to decrease food consumption in rats and that this transient effect is accompanied by changes in brain processes relevant to feeding.

Topics: Animals; Body Weight; Brain; Eating; Gene Expression; Humans; Male; Naltrexone; Oxytocin; Rats

Preterm infants undergo early separation from parents and are exposed to frequent painful clinical procedures, with resultant short- and long-term effects on their neurodevelopment. We aimed to establish whether the mother's voice could provide an effective and safe analgesia for preterm infants and whether endogenous oxytocin (OXT) could be linked to pain modulation. Twenty preterm infants were exposed to three conditions-mother's live voice (speaking or singing) and standard care-in random order during a painful procedure. OXT levels (pg/mL) in saliva and plasma cortisol levels were quantified, and the Premature Infant Pain Profile (PIPP) was blindly coded by trained psychologists. During the mother's live voice, PIPP scores significantly decreased, with a concomitant increase in OXT levels over baseline. The effect on pain perception was marginally significant for singing. No effects on cortisol levels were found. The mother's live voice modulated preterm infants' pain indicators. Endogenous OXT released during vocal contact is a promising protective mechanism during early painful interventions in at-risk populations.

Topics: Adult; Body Weight; Female; Heart Rate; Humans; Infant; Infant Behavior; Infant, Premature; Infant, Premature, Diseases; Mothers; Oxytocin; Pain; Pain Management; Pain Measurement; Saliva; Voice

Experimental allergic encephalomyelitis (EAE) is considered to be a useful animal model of human multiple sclerosis (MS). However, among the various symptoms of MS, the mechanisms contributing to inflammatory anorexia remain unclear. In the present study, we used an EAE rat model to examine changes in expression levels of hypothalamic feeding-related peptide genes and neuroendocrine responses such as the hypothalamo-neurohypophysial system and the hypothalamo-pituitary-adrenal (HPA) axis. The weight gain and cumulative food intake in EAE rats in the early days after immunization was significantly lower than that of the control group. The expression of orexigenic peptide genes Npy and Agrp were significantly increased, whereas the levels of anorectic peptide genes (Pomc and Cart) were significantly decreased in the hypothalamus of EAE rats. There was also a significant increase in the mRNA and plasma oxytocin (OXT) but not of arginine vasopressin (AVP) in the supraoptic and paraventricular nuclei (PVN) of EAE rats at days 12 and 18 after immunization. The expression of corticotropin-releasing hormone (Crh) and Avp was downregulated and upregulated, respectively, in the parvocellular division of the PVN at day 12 after immunization. The expression level of Pomc in the anterior pituitary significantly increased, accompanied by increased plasma corticosterone levels, at days 6, 12, and 18 after immunization. These results suggest that inflammatory anorexia in rat EAE may be caused by activation of the OXT-ergic pathway and HPA axis via changes in the expression of hypothalamic feeding-related peptides, including Avp but not Crh.

Topics: Animals; Arginine Vasopressin; Body Weight; Corticosterone; Eating; Encephalomyelitis, Autoimmune, Experimental; Hypothalamo-Hypophyseal System; Hypothalamus; In Situ Hybridization; Male; Neurophysins; Oxytocin; Pituitary-Adrenal System; Protein Precursors; Rats; Vasopressins

Polycystic ovary syndrome (PCOS) is commonly associated with metabolic disorders, which are exacerbated by obesity. Recent studies have revealed that oxytocin contributes to metabolic, appetite, and body weight regulation. In the present study, we evaluated the effects of chronic administration of oxytocin on body weight, food intake, and fat mass in a dihydrotestosterone-induced rat model of PCOS. Body weight, body weight change, and relative cumulative food intake were significantly lower in the oxytocin-treated PCOS rats than in the vehicle-treated control PCOS rats. Similarly, visceral adipocyte size was significantly smaller in the oxytocin-treated PCOS rats than in the vehicle-treated control PCOS rats. On the other hand, the numbers of cystic follicles in the ovary did not differ between the two groups. The chronic administration of oxytocin did not affect the rats' serum aspartate aminotransferase, alanine aminotransferase, or lactate dehydrogenase levels, indicating that it does not have adverse effects on hepatic function. These findings suggest that oxytocin could be a candidate drug for preventing the onset of obesity-related metabolic disorders in PCOS patients.

Topics: Adipocytes; Alanine Transaminase; Androgens; Animals; Aspartate Aminotransferases; Body Weight; Cell Size; Dihydrotestosterone; Disease Models, Animal; Eating; Female; Intra-Abdominal Fat; L-Lactate Dehydrogenase; Ovarian Cysts; Ovary; Oxytocics; Oxytocin; Polycystic Ovary Syndrome; Rats

The neuropeptide oxytocin is best known for its role during parturition and the milk-let down reflex. Recent evidence identifies a role for oxytocin in eating behaviour. After oxytocin administration, caloric intake is reduced with stronger inhibitory effects in individuals with obesity. Whether the experience of visual food cues affects secretion or circulating levels of oxytocin is unknown. This pilot study had three aims: 1) to measure fasting appetite hormones with a focus on plasma oxytocin concentrations; 2) determine whether healthy vs. hyperpalatable visual food cues differentially altered plasma oxytocin; and 3) assess whether appetite hormone responses to healthy vs. hyperpalatable food images depended on weight or food addiction status. Eighteen healthy women of varying weight status, with/without self-reported food addiction were recruited. Study participants completed a set of standardised questionnaires, including Yale Food Addiction Scale, and attended a one-off experimental session. Blood was collected before and after viewing two sets of food images (healthy and hyperpalatable foods). Participants were randomly allocated in a crossover design to view either healthy images or hyperpalatable foods first. A positive correlation between BMI and plasma oxytocin was found (r

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Case-Control Studies; Cholecystokinin; Cues; Female; Food Addiction; Humans; Middle Aged; Oxytocin; Photic Stimulation; Pilot Projects; Young Adult

Nesfatin-1, processed from nucleobindin-2 (NUCB2), is a potent anorexigenic peptide being expressed in rodent hypothalamic nuclei and involved in the regulation of feeding behavior and body weight in animals. The present study aimed to investigate NUCB2/nesfatin-1 protein expression in the human hypothalamus as well as its correlation with body weight.. Sections of hypothalamus and adjacent cholinergic basal forebrain nuclei, including the nucleus basalis of Meynert (NBM) and the diagonal band of Broca (DBB), from 25 autopsy cases (17 males, 8 females; 8 lean, 9 overweight, 8 obese) were examined using immunohistochemistry and double immunofluorescence labeling.. Prominent NUCB2/nesfatin-1 immunoexpression was detected in supraoptic, paraventricular, and infundibular nuclei, lateral hypothalamic area (LHA)/perifornical region, and NBM/DBB. NUCB2/nesfatin-1 was found to extensively colocalize with (a) oxytocin and vasopressin in paraventricular and supraoptic nuclei, (b) melanin-concentrating hormone in the LHA, and (c) cocaine- and amphetamine-regulated transcript in infundibular and paraventricular nuclei and LHA. Interestingly, in the LHA, NUCB2/nesfatin-1 protein expression was significantly decreased in obese, compared with lean (p < 0.01) and overweight (p < 0.05) subjects.. The findings of the present study are suggestive of a potential role for NUCB2/nesfatin-1 as an integral regulator of food intake and energy homeostasis in the human hypothalamus. In the LHA, an appetite- and reward-related brain area, reduced NUCB2/nesfatin-1 immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and obesity. NUCB2/nesfatin-1 localization in NBM/DBB might imply its participation in the neuronal circuitry controlling cognitive influences on food intake and give impetus towards unraveling additional biological actions of NUCB2/nesfatin-1 in human neuronal networks.

Topics: Adult; Aged; Aged, 80 and over; Body Weight; Case-Control Studies; Female; Humans; Hypothalamic Hormones; Hypothalamus; Male; Melanins; Middle Aged; Nerve Tissue Proteins; Nucleobindins; Obesity; Oxytocin; Pituitary Hormones; Vasopressins

Oxytocin (OT) is a well-characterized neurotransmitter that participates in a wide range of physiological processes including the inhibition of food intake. The avian ortholog, mesotocin (MT), differs from OT by a single amino acid. Little is known regarding the function of OT in regulating energy balance in birds; thus, this study was designed to determine the effects of central OT injection on food intake and adipose tissue physiology in chicks. At 4-d post-hatch, broiler chicks were fasted for 3 h and injected intracerebroventricularly with 0 (vehicle), 0.63, 2.5, 5.0, or 10 nmol OT. Oxytocin decreased food and water intake during the entire 180-min observation period. The reduction in water intake was likely not prandial because chicks that were food restricted after OT injection also drank less. There was increased c-Fos immunoreactivity in several appetite-associated hypothalamic nuclei in OT-injected chicks at 1 h, including the arcuate (ARC), dorsomedial nucleus (DMN), lateral hypothalamus (LH), paraventricular nucleus (PVN), and ventromedial hypothalamus (VMH). OT treatment was associated with reduced hypothalamic corticotropin-releasing factor (CRF) mRNA and increased cloacal temperature at 1 h post-injection. We then investigated appetite- and adipose tissue-associated effects of OT in chicks from lines that have undergone long-term selection for either low (LWS) or high (HWS) juvenile body weight. Central injection of OT decreased food intake in both lines with the magnitude of response greater in the HWS than LWS chicks. Adipose tissue abundance of fatty acid-binding protein 4, monoglyceride lipase (MGLL), MT, and perilipin-1 mRNA was greater in LWS than HWS chicks. Lipoprotein lipase, MGLL, and MT mRNAs increased in response to OT injection in LWS but not HWS chicks. In conclusion, central injection of OT induced anorexia, reduced water intake, increased body temperature, and was associated with activation of the ARC, DMN, LH, PVN, and VMH in the hypothalamus. The effects on appetite and body temperature may involve CRF signaling in the hypothalamus and lipolysis in the adipose tissue, respectively. There were differences in the appetite, and adipose tissue response to OT in body weight-selected lines of chicks supports that MT plays a role in energy balance regulation in chickens.

Topics: Adipose Tissue; Animals; Appetite; Body Temperature; Body Weight; Chickens; Corticotropin-Releasing Hormone; Drinking; Eating; Energy Metabolism; Fasting; Gene Expression; Hypothalamus; Injections, Intraventricular; Oxytocin; Proto-Oncogene Proteins c-fos; RNA, Messenger

Recent studies have shown that oxytocin reduces food intake and body weight gain and promotes lipolysis in some species, including humans. Interestingly, these effects of oxytocin are more marked in obese individuals. Although the menopausal loss of ovarian function induces increased visceral adiposity and some metabolic disorders, no safe medical interventions for these conditions have been established. In this study, we evaluated the effects of oxytocin on appetite, body weight, and fat mass in ovariectomized rats. Six-day oxytocin treatment attenuated cumulative food intake and body weight gain, and reduced visceral and subcutaneous fat weight and adipocyte cell area in ovariectomized rats. Blood examinations indicated that 6-day oxytocin treatment did not alter renal or hepatic functions. Instead, it might prevent ovariectomy-induced liver damage. In addition, acute oxytocin treatment did not affect body temperature or locomotor activity. These results indicate that oxytocin might be useful for treating or preventing menopause-induced metabolic disorders, without causing any adverse effects.

Topics: Adipose Tissue; Animals; Body Weight; Eating; Female; Obesity; Ovariectomy; Oxytocin; Rats

Oxytocin administration to diet-induced obese (DIO) rodents, monkeys and humans decreases body weight and fat mass with concomitant improvements in glucose metabolism. Moreover, several studies show an immunomodulatory role of oxytocin in a number of settings (such as atherosclerosis, injury, sepsis). This study aims to shed some light on the effects of oxytocin on macrophage polarization and cytokine production, as well as its possible impact on these parameters in adipose tissue in DIO mice with impaired glucose metabolism.. Mouse bone marrow cells were differentiated into macrophages and treated with oxytocin. Macrophage proliferation, cytokine secretion and macrophage populations were determined. For experiments in vivo, DIO mice were treated with oxytocin for 2 weeks. Body weight and composition and glucose tolerance were subsequently followed. At the end of treatment, adipose tissue macrophage populations, plasma cytokine levels and cytokine expression in adipose tissue were determined.. In bone marrow-derived macrophages, oxytocin induced an anti-inflammatory phenotype (decreased M1/M2 ratio). In M1-derived macrophages, oxytocin decreased TNFα secretion, with no effects on the other cytokines tested nor any effect on cytokine secretion by M2-derived macrophages. Oxytocin treatment in DIO mice in vivo led to decreased body weight accompanied by an improvement in glucose tolerance, with no changes in plasma cytokine levels. In adipose tissue, oxytocin decreased Tnfα expression without modifying the M1/M2 macrophage ratio.. Oxytocin treatment decreases TNFα production both in vitro (in bone marrow-derived macrophages) and in vivo (in epididymal adipose tissue) in DIO mice. This effect may also be contributory to the observed improvement in glucose metabolism.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Bone Marrow Cells; Macrophages; Mice; Oxytocin; Tumor Necrosis Factor-alpha

Multiple stimulatory and inhibitory neural circuits control eating, and these circuits are influenced by an array of hormonal, neuropeptide, and neurotransmitter signals. For example, estrogen and oxytocin (OT) both are known to decrease food intake, but the mechanisms by which these signal molecules influence eating are not fully understood. These studies investigated the interaction between estrogen and OT in the control of food intake. RT-qPCR studies revealed that 17β-estradiol benzoate (EB)-treated rats showed a two-fold increase in OT mRNA in the paraventricular nucleus of the hypothalamus (PVN) compared to Oil-treated controls. Increased OT mRNA expression may increase OT protein levels, and immunohistochemistry studies showed that EB-treated rats had more intense OT labeling in the nucleus of the solitary tract (NTS), a region known to integrate signals for food intake. Food intake measurements showed that EB treatment reduced food intake, as expected. EB-treated rats lost weight over the course of the experiment, as expected, and EB-treated rats that received the highest dose of OT lost more weight than EB-treated rats that did not receive OT. Finally, OT antagonist administered to EB-treated rats reversed the effect of EB on food intake, suggesting that estrogen effects to decrease food intake may involve the oxytocinergic pathway.

Topics: Animals; Appetite Regulation; Body Weight; Eating; Estradiol; Estrogens; Female; Hypothalamus; Ovariectomy; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Signal Transduction; Solitary Nucleus

Whereas leptin administration only has a negligible effect on the treatment of obesity, it has been demonstrated that its action can be improved by co-administration of leptin and one of its sensitizers. Considering that oxytocin treatment decreases body weight in obese animals and humans, we investigated the effects of oxytocin and leptin cotreatment. First, lean and diet-induced obese (DIO) mice were treated with oxytocin for 2 weeks and we measured the acute leptin response. Second, DIO mice were treated for 2 weeks with saline, oxytocin (50 μg/day), leptin (20 or 40 µg/day) or oxytocin plus leptin. Oxytocin pre-treatment restored a normal acute leptin response, decreasing food intake and body weight gain. Chronic continuous administration of oxytocin or leptin at 40 µg/day decreased body weight in the presence (leptin) or in the absence (oxytocin) of cumulative differences in food intake. Saline or leptin treatment at 20 µg/day had no impact on body weight. Oxytocin and leptin cotreatments had no additional effects compared with single treatments. These results point to the fact that chronic oxytocin treatment improves the acute, but not the chronic leptin response, suggesting that this treatment could be used to improve the short-term satiety effect of leptin.

Topics: Animals; Body Weight; Diet, High-Fat; Eating; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oxytocin

Chronic stress conditions can lead to considerable and extensible changes in physiological and psychological performances, and in emergence of risk for various somatic diseases. On the other hand, the neuropeptide oxytocin is reported to increase the resistance of the organism to stress and modulate activity of autonomic nervous system. Chronic corticosterone administration is used as a rat model for a state observed in terms of chronic stress exposure, when negative feedback mechanism of hypothalamus-pituitary-adrenal axis activity is disrupted. In our study, we aimed to investigate whether chronic administration of oxytocin (10 IU/400μL/day for 14days, s.c.) influenced adrenal gland morphology and activity in adult male Wistar rats during long-term corticosterone administration via drinking water (100mg/L for 21days). We examined the influence of treatments on the levels of adrenal gland hormones, corticosterone, adrenaline and noradrenaline, as well as their response to an acute stress challenge evoked by 15-min forced swimming. In addition, the expression of two main monoamine transporters, the noradrenaline transporter (NAT) and vesicular monoamine transporter 2 (VMAT2) in adrenal medulla was measured in the rats exposed to acute stress. Our results showed that oxytocin treatment prevented corticosterone-induced decrease in body weight gain, attenuated adrenal gland atrophy by increasing glandular weight, and the area of the zona fasciculate and reticularis. Chronic corticosterone intake blunted the response of all measured hormones to acute stress, whereas concomitant oxytocin treatment reversed adrenaline and noradrenaline response to acute stress. Furthermore, in adrenal medulla, oxytocin produced significant vasodilatation and stimulated expression of both catecholamine transporters detected both on mRNA and protein level. Our data suggest that oxytocin, by reducing atrophy of adrenal gland, and by increasing catecholamine storage capacity, may be beneficial in conditions accompanied with high glucocorticoid levels, such as chronic stress exposure.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Body Weight; Catecholamines; Chronic Disease; Corticosterone; Disease Models, Animal; Epinephrine; Hypothalamo-Hypophyseal System; Male; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins; Oxytocin; Pituitary-Adrenal System; Rats; Rats, Wistar; Stress, Psychological; Vesicular Monoamine Transport Proteins

Obesity is considered as a worldwide problem in both males and females. Although many studies have demonstrated the efficiency of oxytocin (Oxt) as an anti-obesity peptide, there is no comparative study of its effect in males and females. This study aims to determine factors (sex, initial body weight, and fat distribution) that may affect the ability of Oxt to regulate body weight (BW). With regard to sex, Oxt reduced BW similarly in males and females under both high fat diet (HFD) and standard chow-fed condition. The BW reduction induced by Oxt correlated with initial BW in male and female mice under HFD conditions. Oxt showed an equal efficacy in fat degradation in both the visceral and subcutaneous fat mass in both males and females fed with HFD. The effect of Oxt on BW reduction was attenuated in standard chow-fed male and female mice. Therefore, our results suggest that administration of Oxt is more effective in reducing BW in subjects with a high initial BW with increased fat accumulation. The present data contains important information for the possible clinical application of Oxt for the treatment of obesity.

Topics: Animals; Body Fat Distribution; Body Weight; Diet, High-Fat; Feeding Behavior; Female; Male; Mice, Inbred C57BL; Oxytocin; Sex Characteristics

Adjuvant therapy is a common therapeutic strategy used for schizophrenia management. Oxytocin has shown promising results as antipsychotic adjuvant in patients with schizophrenia. Although short-term clinical studies have indicated tolerability and no major side-effect manifestation, long-term studies remain needed. In this study, we investigated whether oxytocin chronic administration in rats may lead to brain DNA damage by comet assay. Our results suggest that 21 and 56-day treatment with once daily intraperitoneal oxytocin (0.1, 1.0 and 10.0 mg/kg) may cause substantial DNA damage in hippocampus. We have not found differences on body weight gain. Our findings also point that further clinical and preclinical studies evaluating oxytocin safety after chronic exposure are necessary.

Topics: Animals; Body Weight; DNA Damage; Hippocampus; Male; Oxytocin; Rats; Rats, Wistar

The aim of the present study is to investigate the protective effects of oxytocin (OT) on diabetic neuropathy (DNP) in rats.. Eighteen rats were used to induce diabetes using single dose streptozotocin (STZ, 60 mg/kg). Diabetic DNP was verified by electromyography (EMG) and motor function test on 21st day following STZ injection. Six rats served as naïve control group and received no drug (n = 6). Following EMG, diabetic rats were randomly divided into three groups and administered with either 1 ml/kg saline or 80 μg/kg OT or 160 μg/kg OT intraperitoneally for four weeks. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and glutathione), histological, and immunohistochemical analysis of sciatic nerves (bax, caspase 3, caspase 9, and NGF) were performed.. Diabetic rats developed neuropathy, which was apparent from decreased compound muscle action potentials amplitudes and prolonged distal latency in saline-treated rats (p < 0.001) whereas 160 μg/kg OT significantly improved EMG findings. OT treatment significantly lessened the thickening of perineural fibrosis when compared with saline group (p < 0.001). Besides, OT significantly reduced plasma lipid peroxides (p < 0.05) and increased glutathione levels in diabetic rats (p < 0.001). The sciatic nerves of saline-treated rats showed considerable increase in bax, caspase 3 and caspase 8 expressions (p < 0.001) while OT treatment significantly suppressed these apoptosis markers. Also, OT improved NGF expression in diabetic rats compared to saline group.. Present results demonstrate that OT appears to alleviate harmful effects of hyperglycemia on peripheral neurons by suppressing inflammation, oxidative stress and apoptotic pathways.

Topics: Analysis of Variance; Animals; bcl-2-Associated X Protein; Blood Glucose; Body Weight; Caspase 3; Caspase 8; Diabetic Neuropathies; Disease Models, Animal; Electromyography; Evoked Potentials, Motor; Glutathione; Lipid Peroxides; Male; Motor Activity; Muscle, Skeletal; Nerve Growth Factor; Oxytocics; Oxytocin; Rats; Rats, Sprague-Dawley; Schwann Cells; Sciatic Nerve; Streptozocin

Body fluid homeostasis requires a complex suite of physiological and behavioral processes. Understanding of the role of the central nervous system (CNS) in integrating these processes has been advanced by research employing immunohistochemical techniques to assess responses to a variety of body fluid challenges. Such techniques have revealed sex/estrogen differences in CNS activation in response to hypotension and hypernatremia. In contrast, it has been difficult to conclusively identify specific CNS areas and neurotransmitter systems that are activated by hyponatremia using these techniques. In part, this difficulty is due to the temporal disconnect between the physiological effects of treatments commonly used to deplete body sodium and the behavioral response to such depletion. In some methods, sodium ingestion is delayed in association with increased oxytocin (OT), suggesting an inhibitory role for OT in sodium intake. Urinary sodium loss increases within an hour after treatment with furosemide, a natriuretic-diuretic, but sodium intake is delayed for 18-24h. Accordingly, we hypothesized that acute furosemide-induced sodium loss activates centrally-projecting OT neurons which provide an initial inhibition of sodium intake, and tested this hypothesis in ovariectomized Sprague-Dawley rats with or without estrogen using immunohistochemical methods. Neuronal activation in the hypothalamic paraventricular nuclei (PVN) after administration of furosemide corresponded to the timing of the physiological effects. The activation was not different in estrogen-treated rats, nor did estrogen alter the initial suppression of sodium intake. However, virtually no fos immunoreactive (fos-IR) neurons in the parvocellular PVN were also immunolabeled for OT. Thus, acute sodium loss after furosemide produces neural activation and an early inhibition of sodium intake that does not appear to involve activation of centrally-projecting OT neurons and is not influenced by estrogen.

Topics: Analysis of Variance; Animals; Body Weight; Contraceptive Agents; Drinking; Estradiol; Female; Furosemide; Oncogene Proteins v-fos; Ovariectomy; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Sodium Potassium Chloride Symporter Inhibitors; Sodium, Dietary; Supraoptic Nucleus; Urination; Uterus

Maternal hypertensive disorder is one of the most common and severe medical complications during pregnancy. Epidural analgesia administration is widely used during labor process.. To evaluate the potential advantage or disadvantage of continuous epidural analgesia's on labor and neonates for maternal hypertensive disorder patients comprehensively.. We have retrospectively analyzed 232 patients who diagnosed as maternal hypertensive disorder in our hospital since 2015. Among which, 126 patients including 28 cases of severe preeclampsia were administrated with continuous epidural analgesia (Analgesia group), the other 106 patients were untreated (Control group). We have compared the maternal age, body weight, gestational weeks, period for the first and second labor stage; the incidence of eclampsia, natural labor, cesarean section, forceps delivery and postpartum hemorrhage between these two groups respectively; furthermore, we recorded patients who received oxytocin and antihypertensive treatment during the delivery progress as well as evaluated the neonate body weight, Apgar score and performed umbilical cord blood gas analysis.. Continuous epidural analgesia does not affect the first and second labor stage period (p=0.36), However, there is a significantly higher demand for oxytocin treatment (36.5% Vs 19.8%, p<0.01) and a significantly lower requirement for antihypertensive treatment (22.2% Vs 81.1%, p<0.001) in analgesia group compared to control group. We also notice that the natural delivery ratio in analgesia group is higher than control group and most importantly, continuous epidural analgesia can increase 1min Apgar score and has no other effect on neonates' body weight, umbilical cord blood gas parameters, 5min and 10min Apgar score.. Our result based on a large cohort comprehensive analysis indicates that continuous epidural analgesia can benefit both maternal hypertensive disorder patients and neonates without any side effect.

Topics: Analgesia, Epidural; Analgesia, Obstetrical; Antihypertensive Agents; Apgar Score; Birth Weight; Body Weight; Cesarean Section; Eclampsia; Female; Fetal Blood; Gestational Age; Humans; Hypertension, Pregnancy-Induced; Infant, Newborn; Labor, Obstetric; Maternal Age; Obstetrical Forceps; Oxytocin; Postpartum Hemorrhage; Pregnancy

The neuropeptides oxytocin and vasopressin have been implicated in exercise, as well as monogamy and parental behavior. In this study, we compared behavioral and neuroendocrine effects of access to an exercise wheel vs. the sedentary state typical in lab animal housing. Male prairie voles (Microtus ochrogaster) were studied because of their extensive repertoire of social behaviors including pair bond formation and biparental care, which are influenced by oxytocin and vasopressin. Subjects in one group had access to a running wheel in their cage (wheel), and voluntarily ran approximately 1.5 km/day for six weeks; these animals were compared to males in standard housing conditions (n=10/group). Males allowed to exercise formed partner preferences significantly faster than controls and exhibited fewer oxytocin neurons, as measured by immunohistochemistry in the bed nucleus of the stria terminalis. We observed no differences in terms of anxiety-related behavior, or alloparental responsiveness. Males with a running wheel equipped cage gained more total body weight, and by the end of the six weeks were found to have less subcutaneous fat and larger testes as a percentage of bodyweight. The changes to gonadal regulation and pair-bonding behavior associated with voluntary exercise are discussed in terms of their possible relevance to the natural history of this species.

Topics: Animals; Arvicolinae; Body Weight; Male; Motor Activity; Neurons; Oxytocin; Pair Bond; Physical Conditioning, Animal; Septal Nuclei; Subcutaneous Fat; Testis; Vasopressins

Melanocortin receptor accessory protein 2 (MRAP2) is a transmembrane accessory protein predominantly expressed in the brain. Both global and brain-specific deletion of Mrap2 in mice results in severe obesity. Loss-of-function MRAP2 mutations have also been associated with obesity in humans. Although MRAP2 has been shown to interact with MC4R, a G protein-coupled receptor with an established role in energy homeostasis, appetite regulation and lipid metabolism, the mechanisms through which loss of MRAP2 causes obesity remains uncertain. In this study, we used two independently derived lines of Mrap2 deficient mice (Mrap2(tm1a/tm1a)) to further study the role of Mrap2 in the regulation of energy balance and peripheral lipid metabolism. Mrap2(tm1a/tm1a) mice have a significant increase in body weight, with increased fat and lean mass, but without detectable changes in food intake or energy expenditure. Transcriptomic analysis showed significantly decreased expression of Sim1, Trh, Oxt and Crh within the hypothalamic paraventricular nucleus of Mrap2(tm1a/tm1a) mice. Circulating levels of both high-density lipoprotein and low-density lipoprotein were significantly increased in Mrap2 deficient mice. Taken together, these data corroborate the role of MRAP2 in metabolic regulation and indicate that, at least in part, this may be due to defective central melanocortin signalling.

Topics: Adaptor Proteins, Signal Transducing; Animals; Anxiety; Basic Helix-Loop-Helix Transcription Factors; Behavior, Animal; Body Weight; Cholesterol; Corticotropin-Releasing Hormone; Eating; Energy Metabolism; Lipid Metabolism; Mice; Mice, Knockout; Motor Activity; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Receptor Activity-Modifying Proteins; Repressor Proteins; Thyrotropin-Releasing Hormone

Oxytocin, a hormone most commonly associated with parturition and lactation, may have additional roles in diabetes complications. We determined oxytocin levels in premenopausal women with type 1 diabetes mellitus (T1DM) compared with non-diabetic controls and examined associations of oxytocin with health behaviours, clinical factors, biomarkers, kidney function and bone health. Lower oxytocin was hypothesized for T1DM.. A cross-sectional study of premenopausal women with T1DM (n = 88) from the Wisconsin Diabetes Registry Study, a population-based cohort of incident T1DM cases, and matched non-diabetic controls (n = 74) was conducted.. Women with T1DM had lower oxytocin levels than controls adjusting for caffeine and alcohol use (p = 0.03). Health behaviours associated with oxytocin differed between women with and without T1DM: oxytocin was negatively associated with hormonal contraceptive use (quantified as lifetime contraceptive oestrogen exposure) in women with T1DM (p = 0.003), whereas positively related to hormonal contraceptive use (quantified as never/former/current) in controls (p < 0.001). Oxytocin had a positive association with adiposity (waist-to-hip ratio and leptin) in women with T1DM and a negative relationship with adiposity (weight gain) in controls. In T1DM only, oxytocin was positively associated with caffeine intake (p = 0.01) and negatively associated with alcohol use (p = 0.01). Oxytocin was not related to glycemic control, kidney function or bone health in T1DM.. Oxytocin levels are lower in women with T1DM than matched controls. Oxytocin also has opposing associations with hormonal contraceptives and adiposity in women with and without T1DM. Research is needed to determine if the altered oxytocin milieu in T1DM is associated with oxytocinher health outcomes.

Topics: Adult; Body Weight; Bone Density; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Humans; Kidney Function Tests; Oxytocin; Premenopause; Young Adult

Salt loading (SL) and water deprivation (WD) are experimental challenges that are often used to study the osmotic circuitry of the brain. Central to this circuit is the supraoptic nucleus (SON) of the hypothalamus, which is responsible for the biosynthesis of the hormones, arginine vasopressin (AVP) and oxytocin (OXT), and their transport to terminals that reside in the posterior lobe of the pituitary. On osmotic challenge evoked by a change in blood volume or osmolality, the SON undergoes a function-related plasticity that creates an environment that allows for an appropriate hormone response. Here, we have described the impact of SL and WD compared with euhydrated (EU) controls in terms of drinking and eating behavior, body weight, and recorded physiological data including circulating hormone data and plasma and urine osmolality. We have also used microarrays to profile the transcriptome of the SON following SL and remined data from the SON that describes the transcriptome response to WD. From a list of 2,783 commonly regulated transcripts, we selected 20 genes for validation by qPCR. All of the 9 genes that have already been described as expressed or regulated in the SON by osmotic stimuli were confirmed in our models. Of the 11 novel genes, 5 were successfully validated while 6 were false discoveries.

Topics: Animals; Arginine Vasopressin; Blood Volume; Body Weight; Drinking; Eating; Gene Expression Profiling; Gene Expression Regulation; Male; Oligonucleotide Array Sequence Analysis; Osmolar Concentration; Osmoregulation; Oxytocin; Rats, Sprague-Dawley; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sodium Chloride, Dietary; Supraoptic Nucleus; Time Factors; Transcriptome; Water Deprivation

Oxytocin circuits are implicated in the regulation of appetite and weight. Variants in the oxytocin receptor (OXTR) gene have been associated with bulimic behaviour. This study aimed to investigate the association between the OXTR gene and eating disorders.. We genotyped six single nucleotide polymorphisms, rs53576, rs237879, rs2228485, rs13316193, rs2254298 and rs1042778, located within the OXTR gene in Korean patients with eating disorders using the single-base extension method. We studied a total of 262 women, including 69 patients with anorexia nervosa, 90 patients with bulimia nervosa (BN), and 103 healthy women.. We found a positive association between the G allele of OXTR rs53576 and BN. In the BN group, the G carriers showed a high score on the behavioural inhibition system.. These findings suggest the involvement of the oxytocinergic system in the mechanism that underlies BN.

Topics: Adult; Anorexia Nervosa; Body Weight; Bulimia Nervosa; Female; Genotype; Humans; Middle Aged; Oxytocin; Polymorphism, Single Nucleotide; Receptors, Oxytocin; Young Adult

Obesity prevalence in developed countries has promoted the need to identify the mechanisms involved in control of feeding and energy balance. We have tested the hypothesis that different fats present in diet composition may contribute in body weight gain and body indexes by regulation of oxytocin gene (oxt) expression in hypothalamus and Oleylethanolamide (OEA) levels in plasma. Sprague-Dawley rats were fed two high fat diets, based on corn (HCO) and extra virgin olive oil (HOO) and results were compared to a low fat diet (LF). LC-MS/MS analysis showed an increasing trend of OEA plasma levels in HOO group, although no significant differences were found. However, body weight gain of LF and HOO were similar and significantly lower than HCO. HCO rats also had higher Lee index than HOO. Rats fed HOO diet showed higher levels of hypothalamic oxt mRNA expression, which could indicate that oxytocin may be modulated by dietary lipids.

Topics: Animals; Body Mass Index; Body Weight; Chromatography, High Pressure Liquid; Chromatography, Liquid; Corn Oil; Diet, Fat-Restricted; Diet, High-Fat; Dietary Fats; Male; Obesity; Oleic Acids; Olive Oil; Oxytocin; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tandem Mass Spectrometry; Weight Gain

Intranasal administration of oxytocin (OXT) might be a promising new adjunctive therapy for mental disorders characterized by social behavioral alterations such as autism and schizophrenia. Despite promising initial studies in humans, it is not yet clear the specificity of the behavioral effects induced by chronic intranasal OXT and if chronic intranasal OXT could have different effects compared with single administration. This is critical for the aforementioned chronic mental disorders that might potentially involve life-long treatments. As a first step to address these issues, here we report that chronic intranasal OXT treatment in wild-type C57BL/6J adult mice produced a selective reduction of social behaviors concomitant to a reduction of the OXT receptors throughout the brain. Conversely, acute intranasal OXT treatment produced partial increases in social behaviors towards opposite-sex novel-stimulus female mice, while on the other hand, it decreased social exploration of same-sex novel stimulus male mice, without affecting social behavior towards familiar stimulus male mice. Finally, prolonged exposure to intranasal OXT treatments did not alter, in wild-type animals, parameters of general health such as body weight, locomotor activity, olfactory and auditory functions, nor parameters of memory and sensorimotor gating abilities. These results indicate that a prolonged over-stimulation of a 'healthy' oxytocinergic brain system, with no inherent deficits in social interaction and normal endogenous levels of OXT, results in specific detrimental effects in social behaviors.

Topics: Administration, Intranasal; Animals; Auditory Perception; Body Weight; Brain; Exploratory Behavior; Habituation, Psychophysiologic; Male; Mice; Mice, Inbred C57BL; Motor Activity; Olfactory Perception; Oxytocin; Psychotropic Drugs; Receptors, Oxytocin; Recognition, Psychology; Sensory Gating; Sex Factors; Social Behavior; Time Factors; Time Perception

Osteoporosis and overweight/obesity constitute major worldwide public health burdens that are associated with aging. A high proportion of women develop osteoporosis and increased intraabdominal adiposity after menopause. which leads to bone fractures and metabolic disorders. There is no efficient treatment without major side effects for these 2 diseases. We previously showed that the administration of oxytocin (OT) normalizes ovariectomy-induced osteopenia and bone marrow adiposity in mice. Ovariectomized mice, used as an animal model mimicking menopause, were treated with OT or vehicle. Trabecular bone parameters and fat mass were analyzed using micro-computed tomography. Herein, we show that this effect on trabecular bone parameters was mediated through the restoration of osteoblast/osteoclast cross talk via the receptor activator of nuclear factor-κB ligand /osteoprotegerin axis. Moreover, the daily administration of OT normalized body weight and intraabdominal fat depots in ovariectomized mice. Intraabdominal fat mass is more sensitive to OT that sc fat depots, and this inhibitory effect is mediated through inhibition of adipocyte precursor's differentiation with a tendency to lower adipocyte size. OT treatment did not affect food intake, locomotors activity, or energy expenditure, but it did promote a shift in fuel utilization favoring lipid oxidation. In addition, the decrease in fat mass resulted from the inhibition of the adipose precursor's differentiation. Thus, OT constitutes an effective strategy for targeting osteopenia, overweight, and fat mass redistribution without any detrimental effects in a mouse model mimicking the menopause.

Topics: Adipocytes; Adipose Tissue; Animals; Body Weight; Bone Diseases, Metabolic; Cell Culture Techniques; Coculture Techniques; Disease Models, Animal; Female; Leptin; Lipids; Menopause; Mice; Mice, Inbred C57BL; Osteoblasts; Osteoclasts; Osteoporosis; Ovariectomy; Oxygen; Oxytocin; Weight Gain; X-Ray Microtomography

Social relationships are essential for many fundamental aspects of life while bond disruption can be detrimental to mental and physical health. Male prairie voles form enduring social bonds with their female partners, allowing the evaluation of partner loss on behavior, physiology, and neurochemistry. Males were evaluated for partner preference formation induced by 24h of mating, and half were separated from their partner for 4 wk. In Experiment 1, partner loss significantly increased anxiety-like behaviors in the elevated plus maze and light-dark box tests and marginally increased depressive-like behaviors in the forced swim test. In addition, while intruder-directed aggression is common in pair bonded prairie voles, separated males were affiliative and lacked aggression toward an unfamiliar female and an intruding male conspecific. Partner loss increased the density of oxytocin-immunoreactivity (-ir), vasopressin-ir, and corticotrophin-releasing hormone-ir cells in the paraventricular nucleus of the hypothalamus and oxytocin-ir cells in the supraoptic nucleus. Tyrosine hydroxylase-ir was not affected. In Experiment 2, partner preference was observed after 2 wk of partner loss but eliminated after 4 wk partner loss. Body weight gain and plasma corticosterone concentrations were elevated throughout the 4 wk. No effects were observed for plasma oxytocin or vasopressin. Together, partner loss elicits anxiety-like and depression-like behaviors, disrupts bond-related behaviors, and alters neuropeptide systems that regulate such behaviors. Thus, partner loss in male prairie voles may provide a model to better understand the behavior, pathology, and neurobiology underlying partner loss and grief.

Topics: Adaptation, Ocular; Aggression; Animals; Arginine Vasopressin; Arvicolinae; Body Weight; Brain; Corticosterone; Corticotropin-Releasing Hormone; Male; Maze Learning; Neurochemistry; Oxytocin; Pair Bond; Social Isolation; Stress, Psychological; Swimming; Time Factors; Tyrosine 3-Monooxygenase; Vasopressins

Oxytocin has been implicated in the modulation of energy metabolism in animals. Oxytocin knockout mice develop obesity without a change in food intake, suggesting that a lack of oxytocin may reduce metabolic rate. Furthermore, administration of oxytocin centrally reduces food intake in rats, an effect reversed by an oxytocin antagonist, implying that oxytocin may regulate appetite and energy intake. We have previously demonstrated that young female athletes (in a higher energy expenditure state than nonathletes) have low nocturnal oxytocin compared with nonathletes. Whether oxytocin is associated with measures of energy homeostasis in athletes is unknown.. We hypothesized that oxytocin, a signal for energy availability, would be associated with other measures of energy homeostasis in young female athletes.. We performed a cross-sectional study of 45 females, aged 14-21 years [15 amenorrheic athletes (AA), 15 eumenorrheic athletes, and 15 nonathletes] of comparable body mass index.. Dual x-ray absorptiometry was performed to assess body composition. Indirect calorimetry was used to measure resting energy expenditure (REE). Fasting levels of oxytocin, energy homeostasis hormones irisin and fibroblast growth factor-21, and appetite-regulating hormone peptide YY were obtained.. In AA, oxytocin secretion was positively correlated with surrogate measures of energy availability, including weight (r = 0.65, P = .009) and body mass index (r = 0.61, P = .016). Furthermore, oxytocin was associated with REE (r = 0.80, P = .0003), independent of lean mass, and with irisin (r = 0.74, P = .002) and fibroblast growth factor-21 (r = 0.58, P = .024). In eumenorrheic athletes, oxytocin was associated with REE (r = 0.59, P = .021), independent of lean mass. In nonathletes, oxytocin secretion was not significantly associated with measures of energy homeostasis.. In AA, oxytocin secretion is associated with measures of energy availability and expenditure, suggesting that oxytocin may be involved in regulation of energy balance in energy deficient states. Further studies determining the role of oxytocin in appetite and energy homeostasis in athletes are warranted.

Topics: Adolescent; Amenorrhea; Athletes; Body Mass Index; Body Weight; Calorimetry, Indirect; Cross-Sectional Studies; Energy Metabolism; Female; Fibroblast Growth Factors; Fibronectins; Humans; Oxytocin; Young Adult

Germline haploinsufficiency of human or mouse Sim1 is associated with hyperphagic obesity. Sim1 encodes a transcription factor required for proper formation of the paraventricular (PVN), supraoptic, and anterior periventricular hypothalamic nuclei. Sim1 expression persists in these neurons in adult mice, raising the question of whether it plays a physiologic role in regulation of energy balance. We previously showed that Sim1 heterozygous mice had normal numbers of PVN neurons that were hyporesponsive to melanocortin 4 receptor agonism and showed reduced oxytocin expression. Furthermore, conditional postnatal neuronal inactivation of Sim1 also caused hyperphagic obesity and decreased hypothalamic oxytocin expression. PVN projections to the hindbrain, where oxytocin is thought to act to modulate satiety, were anatomically intact in both Sim1 heterozygous and conditional knockout mice. These experiments provided evidence that Sim1 functions in energy balance apart from its role in hypothalamic development but did not rule out effects of Sim1 deficiency on postnatal hypothalamic maturation. To address this possibility, we used a tamoxifen-inducible, neural-specific Cre transgene to conditionally inactivate Sim1 in adult mice with mature hypothalamic circuitry. Induced Sim1 inactivation caused increased food and water intake and decreased expression of PVN neuropeptides, especially oxytocin and vasopressin, with no change in energy expenditure. Sim1 expression was not required for survival of PVN neurons. The results corroborate previous evidence that Sim1 acts physiologically as well as developmentally to regulate body weight. Inducible knockout mice provide a system for studying Sim1's physiologic function in energy balance and identifying its relevant transcriptional targets in the hypothalamus.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Body Weight; Bone Density Conservation Agents; Eating; Energy Metabolism; Female; Homeostasis; Hyperphagia; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Neurons; Neuropeptides; Obesity; Oxytocin; Paraventricular Hypothalamic Nucleus; Repressor Proteins; Tamoxifen

Dominance hierarchies are an important aspect of group-living as they determine individual access to resources. The existence of dominance ranks in access to space has not been described in socially monogamous, communally nesting prairie voles (Microtus ochrogaster). Here, we tested whether dominance could be assessed using the tube test. We also tested whether dominance related to alcohol intake, similar to what has been demonstrated in nonmonogamous species. Same-sex pairs of unfamiliar peers were tested in a series of three trials of the tube test, then paired and allowed individual access to alcohol and water for 4 days, and then tested again in the tube test. For all pairs, the same subjects won the majority of trials before and after alcohol drinking. The number of wins negatively correlated with alcohol intake on the first day of drinking and positively correlated with levels of Fos in the paraventricular nucleus of the hypothalamus following the tube test in a separate group of voles. Dominance was not related to Fos levels in other brain regions examined. Together, these results indicate that prairie voles quickly establish stable dominance ranks through a process possibly involving the hypothalamus and suggest that dominance is linked to alcohol drinking.

Topics: Aging; Alcohol Drinking; Animals; Arvicolinae; Body Weight; Central Nervous System Depressants; Ethanol; Female; Immunohistochemistry; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Peer Group; Proto-Oncogene Proteins c-fos; Psychological Tests; Social Dominance

Agonistic interactions are a powerful stressor. Conversely, positive social interactions can reduce the adverse effects of social stress. This possibly occurs through the action of oxytocin (OT), a neuropeptide able to reduce activation of the hypothalamo-pituitary-adrenal (HPA) axis. We hypothesized that repeated OT intranasal administration to neonatal pigs could provide long-lasting protective effects against social stress. In each of six litters, two pigs per litter received 0.5 mL of saline containing 24 IU (or 50 μg) of OT intranasally and two control littermates received 0.5 mL of saline as a control at 1, 2 and 3 days of age. Contrary to our predictions, when socially mixed after weaning at 17 days of age, neonatally OT-administered pigs received more aggressive interactions and performed more aggressive interactions in return, showed greater locomotion, spent less time in social contact, and had greater cortisol concentrations than control pigs. When this social mixing was repeated at 8 weeks of age, OT pigs still performed more aggressive interactions and had greater adrenocorticotropic hormone concentrations than control pigs. A dexamethasone suppression test and corticotropic releasing hormone administration challenge at 11 weeks of age revealed that OT pigs were less responsive to dexamethasone than control pigs, suggesting a deficient HPA axis' negative feedback control. Postnatal repeated OT administration altered social behavior and resulted in a long-term dysregulation of the HPA axis. These findings highlight the complex, fine-tuning of the neurobiological mechanisms regulating the development of social behavior and suggest caution in the application of neonatal peptide treatments during early development.

Topics: Administration, Intranasal; Aggression; Animals; Animals, Newborn; Body Weight; Corticotropin-Releasing Hormone; Dexamethasone; Drug Administration Schedule; Female; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Motor Activity; Oxytocics; Oxytocin; Pituitary-Adrenal System; Social Behavior Disorders; Social Dominance; Sucking Behavior; Swine; Time Factors; Weaning

The adipocyte-derived hormone leptin acts in the brain to reduce body weight and fat mass. Recent studies suggest that parvocellular oxytocin (OXT) neurons of the hypothalamic paraventricular nucleus (PVN) can mediate body weight reduction through inhibition of food intake and increased energy expenditure. However, the role of OXT neurons of the PVN as a primary target of leptin has not been investigated. Here, we studied the potential role of OXT neurons of the PVN in leptin-mediated effects on body weight regulation in fasted rats. We demonstrated that intracerebroventricular (ICV) leptin activates STAT3 phosphorylation in OXT neurons of the PVN, showed that this occurs in a subpopulation of OXT neurons that innervate the nucleus of the solitary tract (NTS), and provided further evidence suggesting a role of OXT to mediate leptin's actions on body weight. In addition, our results indicated that OXT neurons are responsive to ICV leptin and mediate leptin effects on body weight in diet induced obese (DIO) rats, which are resistant to the anorectic effects of the hormone. Thus, we conclude that leptin targets a specific subpopulation of parvocellular OXT neurons of the PVN, and that this action may be important for leptin's ability to reduce body weight in both control and obese rats.

Topics: Analysis of Variance; Animals; Body Weight; DNA Primers; Gene Expression Profiling; Immunohistochemistry; Infusions, Intraventricular; Leptin; Male; Neurons; Obesity; Oxytocin; Paraventricular Hypothalamic Nucleus; Phosphorylation; Rats; Rats, Sprague-Dawley; STAT3 Transcription Factor; Stilbamidines

The prevalence of neurodevelopmental disorders such as autism is increasing, however the etiology of these disorders is unclear and thought to involve a combination of genetic, environmental and immune factors. A recent epidemiological study found that gestational viral exposure during the first trimester increases risk of autism in offspring by twofold. In mice gestational viral exposures alter behavior of offspring, but the biological mechanisms which underpin these behavioral changes are unclear. We hypothesized that gestational viral exposure induces changes in affiliative hormones, brainstem autonomic nuclei and neurotransmitters which are associated with behavioral alterations in offspring. To address this hypothesis, we exposed pregnant mice to influenza A virus (H3N2) on gestational day 9 and determined behavioral, hormonal and brainstem changes in male and female offspring. We found that gestational flu exposure induced dose-dependent alterations in social and aggressive behaviors (p≤0.05) in male and female offspring and increases in locomotor behaviors particularly in male offspring (p≤0.05). We found that flu exposure was also associated with reductions in oxytocin and serotonin (p≤0.05) levels in male and female offspring and sex-specific changes in dopamine metabolism. In addition we found changes in catecholaminergic and microglia density in brainstem tissues of male flu exposed offspring only (p≤0.05). This study demonstrates that gestational viral exposure induces behavioral changes in mice, which are associated with alterations in affiliative hormones. In addition we found sex-specific changes in locomotor behavior, which may be associated with sex-specific alterations in dopamine metabolism and brainstem inflammation. Further investigations into maternal immune responses are necessary to unravel the molecular mechanisms which underpin abnormal hormonal, immune and behavioral responses in offspring after gestational viral exposure.

Topics: Animals; Autistic Disorder; Blood Glucose; Body Weight; Brain Stem; Chromatography, High Pressure Liquid; Female; Inflammation; Influenza A Virus, H3N2 Subtype; Male; Maternal Exposure; Mice; Mice, Inbred BALB C; Motor Activity; Orthomyxoviridae Infections; Oxytocin; Pilot Projects; Pregnancy; Random Allocation; Stereotyped Behavior; Testosterone

Maternal mood disorders such as depression and chronic anxiety can negatively affect the lives of both mothers and their adult offspring. An active focus of maternal depression and anxiety research has been the role of chronic social stress in the development of these disorders. Chronic exposure to social stress is common in humans, especially in lactating mothers, and postpartum mood disorders have been correlated with high levels of social conflict and low levels of social support. Recent studies have described an effective and ethologically relevant chronic social stress (CSS) based rodent model for postpartum depression and anxiety. Since CSS attenuates maternal behavior and impairs both dam and offspring growth, it was hypothesized that CSS is an ethologically relevant form of early life stress for the developing female offspring and may have effects on subsequent adult maternal behavior and neuroendocrinology. Dams exposed to early life CSS as infants display substantial increases in pup retrieval and nursing behavior that are specifically associated with attenuated oxytocin, prolactin, and vasopressin gene expression in brain nuclei involved in the control of maternal behavior. Since the growth patterns of both groups were similar despite substantial increases in nursing duration, the early life CSS dams exhibited an attenuated nursing efficiency. It is concluded that early life CSS has long term effects on the neuroendocrinology of maternal care (oxytocin and prolactin) which results in decreased nursing efficiency in the adult dams. The data support the use of early life CSS as an effective model for stress-induced impairments in nursing, such as those associated with postpartum depression and anxiety.

Topics: Aggression; Animals; Arginine Vasopressin; Body Weight; Brain; Female; Gene Expression; Male; Maternal Behavior; Oxytocin; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Receptors, Prolactin; Stress, Psychological

Relaxin-3 is a neuropeptide that is abundantly expressed by discrete brainstem neuron populations that broadly innervate forebrain areas rich in the relaxin-3 G-protein-coupled-receptor, RXFP3. Acute and subchronic central administration of synthetic relaxin-3 or an RXFP3-selective agonist peptide, R3/I5, increase feeding and body weight in rats. Intrahypothalamic injection of relaxin-3 also increases feeding. In this study, we developed a recombinant adeno-associated virus 1/2 (rAAV1/2) vector that drives expression and constitutive secretion of bioactive R3/I5 and assessed the effect of intrahypothalamic injections on daily food intake and body weight gain in adult male rats over 8 weeks. In vitro testing revealed that the vector rAAV1/2-fibronectin (FIB)-R3/I5 directs the constitutive secretion of bioactive R3/I5 peptide. Bilateral injection of rAAV1/2-FIB-R3/I5 vector into the paraventricular nucleus produced an increase in daily food intake and body weight gain (P<0.01, ~23%, respectively), relative to control treatment. In a separate cohort of rats, quantitative polymerase chain reaction analysis of hypothalamic mRNA revealed strong expression of R3/I5 transgene at 3 months post-rAAV1/2-FIB-R3/I5 infusion. Levels of mRNA transcripts for the relaxin-3 receptor RXFP3, the hypothalamic 'feeding' peptides neuropeptide Y, AgRP and POMC, and the reproductive hormone, GnRH, were all similar to control, whereas vasopressin and oxytocin (OT) mRNA levels were reduced by ~25% (P=0.051) and ~50% (P<0.005), respectively, in rAAV1/2-FIB-R3/I5-treated rats (at 12 weeks, n=9/8 rats per group). These data demonstrate for the first time that R3/I5 is effective in modulating feeding in the rat by chronic hypothalamic RXFP3 activation and suggest a potential underlying mechanism involving altered OT signalling. Importantly, there was no desensitization of the feeding response over the treatment period and no apparent deleterious health effects, indicating that targeting the relaxin-3-RXFP3 system may be an effective long-term therapy for eating disorders.

Topics: Animals; Body Weight; Dependovirus; Disease Models, Animal; Eating; Feeding and Eating Disorders; Feeding Behavior; Fibronectins; HEK293 Cells; Humans; Hypothalamus; Male; Nerve Tissue Proteins; Oxytocin; Peptides; Rats; Receptors, G-Protein-Coupled; Receptors, Peptide; Relaxin

The naked mole-rat is a subterranean colonial rodent. In each colony, which can grow to as many as 300 individuals, there is only one female and 1-3 males that are reproductive and socially dominant. The remaining animals are reproductively suppressed subordinates that contribute to colony survival through their cooperative behaviors. Oxytocin is a peptide hormone that has shown relatively widespread effects on prosocial behaviors in other species. We examined whether social status affects the number of oxytocin-immunoreactive neurons in the paraventricular nucleus and the supraoptic nucleus by comparing dominant breeding animals to subordinate non-breeding workers from intact colonies. We also examined these regions in subordinate animals that had been removed from their colony and paired with an opposite- or same-sex conspecific for 6 months. Stereological analyses indicated that subordinates had significantly more oxytocin neurons in the paraventricular nucleus than breeders. Animals in both opposite- and same-sex pairs showed a decreased oxytocin neuron number compared to subordinates suggesting that status differences may be due to social condition rather than the reproductive activity of the animal per se. The effects of social status appear to be region specific as no group differences were found for oxytocin neuron number in the supraoptic nucleus. Given that subordinate naked mole-rats are kept reproductively suppressed through antagonism by the queen, we speculate that status differences are due either to oxytocin's anxiolytic properties to combat the stress of this antagonism or to its ability to promote the prosocial behaviors of subordinates.

Topics: Age Factors; Analysis of Variance; Animals; Body Weight; Cell Count; Female; Hypothalamus; Male; Mole Rats; Neurons; Oxytocin; Social Conditions

Smooth muscle α-actin (Acta2) is one of six highly conserved mammalian actin isoforms that appear to exhibit functional redundancy. Nonetheless, we have postulated a specific functional role for the smooth muscle specific isoform. Here, we show that Acta2 deficient mice have a remarkable mammary phenotype such that dams lacking Acta2 are unable to nurse their offspring effectively. The phenotype was rescued in cross fostering experiments with wild type mice, excluding a developmental defect in Acta2 null pups. The mechanism for the underlying phenotype is due to myoepithelial dysfunction postpartum resulting in precocious involution. Further, we demonstrate a specific defect in myoepithelial cell contractility in Acta2 null mammary glands, despite normal expression of cytoplasmic actins. We conclude that Acta2 specifically mediates myoepithelial cell contraction during lactation and that this actin isoform therefore exhibits functional specificity.

Topics: Actins; Animals; Animals, Newborn; Apoptosis; Body Weight; Cells, Cultured; Epithelial Cells; Female; Gene Expression; Immunoblotting; Lactation; Male; Mammary Glands, Animal; Maternal Behavior; Mice; Mice, 129 Strain; Mice, Inbred BALB C; Mice, Knockout; Oxytocics; Oxytocin; Pregnancy; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction

The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, Sprague-Dawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 1-20). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured before and after testing throughout the test day, whereas plasma and brain oxytocin concentrations were measured post-testing only. The results obtained indicated increased CORT response after the OFT in CC-treated dams (P ≤ 0.05). CC-treated dams also exhibited altered FST behaviour (P ≤ 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (P ≤ 0.05). Peripheral oxytocin and CORT increased after the FST, regardless of treatment condition (P ≤ 0.05). Changes in stress-responsiveness, both behaviourally and hormonally, may underlie some deficits in maternal behaviour; thus, a clearer understanding of the effect of CC on the stress response system may potentially lead to treatment interventions that could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations.

Topics: Animals; Body Weight; Brain; Cocaine; Corticosterone; Disease Models, Animal; Female; Immobility Response, Tonic; Male; Motor Activity; Oxytocin; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Stress, Psychological

Oxytocin (OT) is essentially associated with uterine contraction during parturition and milk ejection reflex. Although several studies implicate the role of OT in anti-inflammatory, anti-oxidative and anti-apoptotic pathways, there is a lack of data with regard to the protective effects of oxytocin in neurodegenerative models such as Parkinson's disease (PD). The present study was undertaken to investigate the neuroprotective effects of oxytocin (OT) on rotenone-induced PD in rats. Twenty adult Sprague-Dawley rats were injected with rotenone (3 μg/μl in DMSO) or vehicle (1 μl DMSO) into the left substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) under stereotaxic surgery, and PD model was assessed by rotational test ten days after drug infusion. The valid PD rats were randomly divided into two groups; Group 1 (n=7) and Group 2 (n=7) were administered saline (1 ml/kg/day, i.p.) and oxytocin (160 μg/kg/day, i.p.) through 20 days, respectively. The effects of OT treatment were evaluated by behavioral, histological and immunohistochemical parameters. Apomorphine-induced stereotypic rotations in PD rats were significantly inhibited by OT treatment (p<0.05). In addition, immunohistochemical studies clearly demonstrated the suppression of Bax, caspase-3, caspase-8 and elevation of Bcl-2 and tyrosine hydroxylase immunoexpression in OT-treated rats compared to saline group. Our findings suggest that oxytocin may have cytoprotective and restorative effects on dopaminergic neurons against rotenone-induced injury. The underlying mechanism may be associated with the inhibition of apoptotic pathways.

Topics: Animals; Apomorphine; Behavior, Animal; Body Weight; Cell Death; Dopaminergic Neurons; Male; Neostriatum; Oxytocin; Parkinson Disease; Rats; Rats, Sprague-Dawley; Rotenone

Oxytocin neurons represent one of the major subsets of neurons in the paraventricular hypothalamus (PVH), a critical brain region for energy homeostasis. Despite substantial evidence supporting a role of oxytocin in body weight regulation, it remains controversial whether oxytocin neurons directly regulate body weight homeostasis, feeding or energy expenditure. Pharmacologic doses of oxytocin suppress feeding through a proposed melanocortin responsive projection from the PVH to the hindbrain. In contrast, deficiency in oxytocin or its receptor leads to reduced energy expenditure without feeding abnormalities. To test the physiological function of oxytocin neurons, we specifically ablated oxytocin neurons in adult mice. Our results show that oxytocin neuron ablation in adult animals has no effect on body weight, food intake or energy expenditure on a regular diet. Interestingly, male mice lacking oxytocin neurons are more sensitive to high fat diet-induced obesity due solely to reduced energy expenditure. In addition, despite a normal food intake, these mice exhibit a blunted food intake response to leptin administration. Thus, our study suggests that oxytocin neurons are required to resist the obesity associated with a high fat diet; but their role in feeding is permissive and can be compensated for by redundant pathways.

Topics: Animals; Body Weight; Diet, High-Fat; Dietary Fats; Eating; Energy Intake; Energy Metabolism; Homeostasis; Injections, Intraperitoneal; Leptin; Male; Mice; Mice, Transgenic; Neurons; Obesity; Oxytocin; Paraventricular Hypothalamic Nucleus

Adolescent development is proposed to represent a time of increased susceptibility to stress. During adolescence, the brain demonstrates a high level of plasticity and can be positively or negatively affected by the environment. This study tests the hypothesis that adolescent development is a stage of enhanced vulnerability to chronic stress. Male Sprague-Dawley rats were exposed to our 14-d chronic variable stress (CVS) paradigm at three developmental stages: 1) early adolescence (35 d; age at initiation of CVS); 2) late adolescence (50 d); or 3) adulthood (80 d). We examined the effects of CVS on the following: 1) depression-like behavior; 2) somatic indices; 3) hypothalamic-pituitary-adrenal (HPA) axis activity; and 4) neuropeptide expression in the hypothalamus. Results show, regardless of age, CVS exposure: 1) decreased body weight; 2) increased adrenal size; 3) decreased fat weight; and 4) increased HPA response to stress. The somatic effects of CVS were exaggerated in late adolescent animals, and late adolescent animals were the only group where CVS decreased oxytocin expression and increased basal corticosterone. In response to CVS, adult animals increased immobility during the forced-swim test while early and late adolescent animals were resistant to the effects of chronic stress on depression-like behavior. Results show that adolescent animals were protected from the effect of chronic stress on depression-like behavior while late adolescent animals were more susceptible to the somatic, HPA axis, and neuropeptide effects of chronic stress. Thus, adolescent development is a unique window of vulnerabilities and protections to the effects of chronic stress.

Topics: Animals; Arginine Vasopressin; Body Composition; Body Weight; Corticosterone; Corticotropin-Releasing Hormone; Hypothalamo-Hypophyseal System; In Situ Hybridization; Male; Oxytocin; Pituitary-Adrenal System; Rats; Rats, Sprague-Dawley; Stress, Physiological

Hypothalamic neuropeptides play essential roles in regulating energy and body weight balance. Energy imbalance and obesity have been linked to hypothalamic signaling defects in regulating neuropeptide genes; however, it is unknown whether dysregulation of neuropeptide exocytosis could be critically involved. This study discovered that synaptotagmin-4, an atypical modulator of synaptic exocytosis, is expressed most abundantly in oxytocin neurons of the hypothalamus. Synaptotagmin-4 negatively regulates oxytocin exocytosis, and dietary obesity is associated with increased vesicle binding of synaptotagmin-4 and thus enhanced negative regulation of oxytocin release. Overexpressing synaptotagmin-4 in hypothalamic oxytocin neurons and centrally antagonizing oxytocin in mice are similarly obesogenic. Synaptotagmin-4 inhibition prevents against dietary obesity by normalizing oxytocin release and energy balance under chronic nutritional excess. In conclusion, the negative regulation of synaptotagmin-4 on oxytocin release represents a hypothalamic basis of neuropeptide exocytosis in controlling obesity and related diseases.

Topics: Animals; Body Weight; Energy Metabolism; Exocytosis; Hypothalamus; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuropeptides; Obesity; Oxytocin; Synaptotagmins

The obesity pandemic can be viewed as a result of an imbalanced reaction to changing environmental factors. Recent research has linked circadian arrhythmicity to obesity and related diseases; however, the underlying mechanisms are still unclear. In this study, we found that high-fat diet (HFD) feeding strikingly promoted daytime rather than nighttime caloric intake in mice, leading to feeding circadian arrhythmicity. Using scheduled feeding with a defined amount of daily HFD intake, we found that an increase in the ratio of daytime to nighttime feeding promoted weight gain, whereas a decrease of this ratio rebalanced energy expenditure to counteract obesity. In identifying the underlying mechanism, we found that hypothalamic release of anorexigenic neuropeptide oxytocin displayed a diurnal rhythm of daytime rise and nighttime decline, which negatively correlated with the diurnal feeding activities of normal chow-fed mice. In contrast, chronic HFD feeding abrogated oxytocin diurnal rhythmicity, primarily by suppressing daytime oxytocin rise. Using pharmacological experiments with hypothalamic injection of oxytocin or oxytocin antagonist, we showed that daytime manipulation of oxytocin can change feeding circadian patterns to reprogram energy expenditure, leading to attenuation or induction of obesity independently of 24-h caloric intake. Also importantly, we found that peripheral injection of oxytocin activated hypothalamic oxytocin neurons to release oxytocin, and exerted metabolic effects similar to central oxytocin injection, thus offering a practical clinical avenue to use oxytocin in obesity control. In conclusion, resting-stage oxytocin release and feeding activity represent a critical circadian mechanism and therapeutic target for obesity.

Topics: Animals; Body Weight; Circadian Rhythm; Energy Intake; Feeding Behavior; Feeding Methods; Injections, Intraventricular; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oxytocics; Oxytocin; Rest

Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Body Weight; Diet; Dose-Response Relationship, Drug; Endocannabinoids; Gene Knockout Techniques; Insulin Resistance; Male; Mice; Obesity; Oleic Acids; Oxytocin; PPAR alpha; Rats

Previous studies have suggested that administration of oxytocin (OT) can have modulatory effects on social and anxiety-like behavior in mammals that may endure beyond the time of acute OT administration. The current study examined whether repeated administration of OT to male Wistar rats (n = 48) during a key developmental epoch (early adolescence) altered their physiology and behavior in later-life. Group housed rats were given intraperitoneal injections of either 1 mg/kg OT or vehicle during early adolescence (post natal-days [PND] 33-42). OT treatment caused a transient inhibition of body weight gain that recovered quickly after the cessation of treatment. At PND 50, the rats pre-treated with OT displayed less anxiety-like behavior on the emergence test, while at PND 55 they showed greater levels of social interaction. A subgroup of OT pre-treated rats examined at PND 63 showed a strong trend towards increased plasma OT levels, and also displayed significantly increased OT receptor mRNA in the hypothalamus. Rats pre-treated with OT and their controls showed similar induction of beer intake in daily 70 min test sessions (PND 63 onwards) in which the alcohol concentration of beer was gradually increased across days from 0.44% to 4.44%. However, when given ad libitum access to beer in their home cages from PND 72 onwards (early adulthood), consumption of beer but not water was significantly less in the OT pre-treated rats. A "booster" shot of OT (1 mg/kg) given after 25 days of ad libitum access to beer had a strong acute inhibitory effect on beer intake without affecting water intake. Overall these results suggest that exogenous OT administered during adolescence can have subtle yet enduring effects on anxiety, sociability and the motivation to consume alcohol. Such effects may reflect the inherent neuroplasticity of brain OT systems and a feed-forward effect whereby exogenous OT upregulates endogenous OT systems.

Topics: Alcohol Drinking; Animals; Anxiety; Beer; Body Weight; Gene Expression Regulation; Interpersonal Relations; Male; Oxytocin; Rats; Rats, Wistar; Receptors, Oxytocin; Time Factors

Subcutaneous administration of oxytocin (OT) increases water intake and sodium/urine excretion in food-deprived male rats. This study analyzes the effect of OT administration (at 0830 and 1430h) on the consumption of water and hypertonic NaCl (1.5%). In the first experiment, injections of OT increased the intake of hypertonic NaCl (but not of water) in food-deprived rats but not in ad lib-fed animals during the second 12 h (2030 to 0830) of the treatment day. The net concentration of the fluid consumed by OT/deprived animals was close to isotonic. In the second experiment, the initial effect of OT administration was an increase in urine volume and urinary sodium excretion and concentration by food-deprived animals during the first 12 h (0830 to 2030). These findings suggest that in food-deprived animals, systemic administration of OT induces NaCl intake as a consequence of previous urine loss and urinary sodium excretion.

Topics: Analysis of Variance; Animals; Body Weight; Drinking Behavior; Feeding Behavior; Food Deprivation; Male; Natriuretic Agents; Oxytocin; Random Allocation; Rats; Rats, Wistar; Saline Solution, Hypertonic; Sodium; Time Factors; Urine; Water

The effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on brain monoamines and the serum level of hormones involved in milk synthesis and on the milk ejection reflex in rats were evaluated. Dams were treated with 2.5, 5, 15, 25, 50 or 70mg 2,4-D/kg bw according to two experimental designs: (a) through food from post partum day 1 (PPD 1) to PPD 16 and the respective control groups or (b) an unique i.p. injection on PPD 11. To measure milk ejection, the litter was separated from the mother at the 11th day of lactation during 8h, returned to their mothers and allowed to suckle for a period of 15min. The procedure was repeated on 3 consecutive days until the end of treatment. The change in litter weight during the suckling period was taken as a measure of the amount of milk ejected during this period. The dams' serum prolactin (PRL), oxytocin (OT) and growth hormone levels were determined by radioimmunoassay. Both treatment regimens produced a dose-dependent decrease in the amount of milk ejected and circulating PRL and OT secreted in response to the suckling stimulus. Administration of OT before returning the pups restored the milk ejection, indicating no impairment in the capacity of the mammary gland to produce and secrete milk. In addition, dopamine levels were increased by the 2,4-D treatments in arcuate nucleus (ArN) and anterior lobe of pituitary gland (AL), while serotonin level was drastically decreased in ArN. 2,4-D treatment increased both calcium-dependent and calcium-independent nitric oxide synthase (NOS) activities in ArN. These results suggest that 2,4-D inhibits the suckling-induced hormone release, milk transfer to the litter at the central level, through a stimulation of hypothalamic NOS and dopamine and by an inhibition of hypothalamic serotonin transmission.

Topics: 2,4-Dichlorophenoxyacetic Acid; Animals; Animals, Suckling; Biogenic Monoamines; Body Weight; Brain; Female; Growth Hormone; Herbicides; Lactation; Male; Milk Ejection; Nitric Oxide Synthase; Organ Size; Oxytocin; Prolactin; Random Allocation; Rats; Rats, Wistar; Statistics, Nonparametric

The alarming increase in childhood, adolescent and adult obesity has exposed the need for understanding early factors affecting obesity and for treatments that may help prevent or moderate its development. In the present study, we used the OLETF rat model of early-onset hyperphagia induced obesity, which become obese as a result of the absence of CCK(1) receptors, to examine the influence of partial food restriction on peripheral adiposity-related parameters during and after chronic and early short-term food restriction. Pair feeding (to the amount of food eaten by control, LETO rats) took place from weaning until postnatal day (PND) 45 (early) or from weaning until PND90 (chronic). We examined fat pad weight (brown, retroperitoneal, inguinal and epididymal); inguinal adipocyte size and number; and plasma leptin, oxytocin and creatinine levels. We also examined body weight, feeding efficiency and spontaneous intake after release from food-restriction. The results showed that chronic food restriction produced significant reductions in adiposity parameters, hormones and body weight, while early food restriction successfully reduced long-term body weight, intake and adiposity, without affecting plasma measurements. Early (and chronic) dieting produced promising long-term effects that may imply the reorganization of both peripheral and central mechanisms that determine energy balance and further support the theory suggesting that early interventions may effectively moderate obesity, even in the presence of a genetic tendency.

Topics: Adipocytes; Adipose Tissue; Adiposity; Animals; Body Weight; Caloric Restriction; Cell Count; Cell Size; Creatinine; Eating; Hyperphagia; Leptin; Male; Obesity; Oxytocin; Rats; Rats, Inbred OLETF

We examined the effects of NaCl injections on the polydipsia and polyuria induced by subcutaneous oxytocin (OT) administration in food-deprived male rats. During the first 12 h of the treatment day, both food deprivation and OT administration increased urine excretion but reduced water intake, water balance (fluid intake minus urine volume) and body weight. OT treatment enhanced urine excretion and the reduction in water balance and body weight without reducing the water intake of food-deprived animals. Analysis of the physiological effects of OT administration showed increases in urinary sodium concentration, sodium excretion and a reduced plasma sodium concentration. During the second 12 h, OT increased both urine excretion and water intake in food-deprived but not in ad lib.-fed rats. However, hypertonic NaCl administration at the start of this second 12-h period blocked the polyuric and polydipsic responses observed in the OT/deprived group but increased the water intake of the ad lib. groups. After the whole 24-h period, animals treated with OT showed a water balance and body weight change matching those observed in Control animals. Although the recording time period is a critical factor to demonstrate the effect of peripheral OT administration on water intake, the results obtained suggest that the polyuric and polydipsic responses observed in food-deprived animals depend on the negative sodium and water balance induced by the natriuretic effect of OT and the unavailability of sodium. These OT-induced deficits can be counteracted by the administration of hypertonic NaCl solutions or simply by the intake of standard food.

Topics: Animals; Body Weight; Drinking; Drinking Behavior; Eating; Food Deprivation; Male; Oxytocin; Polyuria; Rats; Rats, Wistar; Sodium Chloride

There has been little investigation of the possible lasting adverse effects of γ-hydroxybutyrate (GHB).. This study aims to study whether GHB produces residual adverse effects on memory and social behaviour in rats and lasting changes in brain monoamines and oxytocin-related gene expression.. Rats received daily intraperitoneal injections of GHB (500 mg/kg), methylenedioxymethamphetamine (MDMA; 5 mg/kg) or their combination (GHB/MDMA) over ten consecutive days. Locomotor activity and body weight were assessed during the dosing period and withdrawal-related anxiety was assessed 24 h after drug cessation. After a washout of 4 weeks, rats were tested on the emergence, social interaction, and object recognition tasks over a 2-week period. Monoamine levels in cortex and striatum, and hypothalamic oxytocin and oxytocin receptor mRNA, were then assessed.. MDMA and GHB/MDMA caused modest sensitization of locomotor activity over time, while sedative effects of GHB diminished with repeated exposure. GHB-treated rats showed reduced social interaction 24 h after the final dose, indicating GHB withdrawal-induced anxiety. All drug-treated groups displayed residual deficits in social interaction and object recognition. No changes in monoamine levels were detected 8 weeks post-drug. However, MDMA pre-exposure increased hypothalamic oxytocin mRNA while GHB pre-exposure upregulated oxytocin receptor mRNA. GHB/MDMA pre-exposure caused intermediate changes in both of these measures.. GHB treatment caused residual impairments in memory and social behaviour and increases in anxiety, paralleling the lasting adverse effects of MDMA. Both drugs caused lasting neuroadaptations in brain oxytocin systems and this may be related to the long-term social interaction deficiencies caused by both drugs.

Topics: Animals; Anxiety; Behavior, Animal; Biogenic Monoamines; Body Weight; Brain; Chromatography, High Pressure Liquid; Emotions; Gene Expression Regulation; Injections, Intraperitoneal; Male; Memory; Motor Activity; N-Methyl-3,4-methylenedioxyamphetamine; Oxytocin; Polymerase Chain Reaction; Rats; Rats, Wistar; Receptors, Oxytocin; Recognition, Psychology; RNA, Messenger; Social Behavior; Sodium Oxybate; Substance Withdrawal Syndrome; Time Factors

Obesity and the metabolic syndrome represent serious health threats affecting increasing numbers of individuals, with females being more affected than males and with growing incidence among children and adolescents. In the present study, we used the OLETF rat model of early-onset obesity to examine the influence of different timing of food restriction on long-term obesity levels in females. Food restriction took place at different time windows: from weaning until postnatal day (PND) 45 (early); from weaning until PND90 (chronic); or from PND45 until PND70 (late). Follow-up continued until PND90. During and after the termination of the diet-restriction period, we focused on peripheral adiposity-related measures such as fat pad weight (brown, retroperitoneal and inguinal); inguinal adipocyte size and number; and leptin, oxytocin and glucose levels. We also examined body weight, feeding efficiency, spontaneous intake after release from diet-restriction, and plasma creatinine levels and estrous cycle characteristics as a result of the chronic diet. The results suggest that while food restriction produced significant weight and adiposity loss, OLETF females presented poor weight loss retention after the early and late short-term diets. The estrous cycle structure and time of first estrous of the OLETF rats were normalized by chronic food restriction. Females responded to early food restriction in a different manner than males did in previous studies, further emphasizing the importance of sex-appropriate approaches in the investigation and treatment of the pathologies related to obesity and the metabolic syndrome.

Topics: Adipocytes; Adiposity; Animals; Body Weight; Caloric Restriction; Cell Count; Cell Size; Eating; Female; Leptin; Male; Obesity; Oxytocin; Rats; Rats, Inbred OLETF; Time Factors; Weaning

Topics: Adiponectin; Adiposity; Animals; Body Weight; Humans; Neurons; Obesity; Oxytocin; Paraventricular Hypothalamic Nucleus; Thyrotropin-Releasing Hormone

Arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) in the parvocellular neurosecretory cells of the paraventricular nucleus (PVN) play a major role in activating the hypothalamic-pituitary-adrenal axis, which is the main neuroendocrine response against the many kinds of stress. We examined the effects of chronic inflammatory/nociceptive stress on the expression of the AVP-enhanced green fluorescent protein (eGFP) fusion gene in the hypothalamus, using the adjuvant arthritis (AA) model. To induce AA, the AVP-eGFP rats were intracutaneously injected heat-killed Mycobacterium butyricum (1 mg/rat) in paraffin liquid at the base of their tails. We measured AVP, oxytocin and corticosterone levels in plasma and changes in eGFP and CRH mRNA in the hypothalamus during the time course of AA development. Then, we examined eGFP fluorescence in the PVN, the supraoptic nucleus (SON), median eminence (ME) and posterior pituitary gland (PP) when AA was established. The plasma concentrations of AVP, oxytocin and corticosterone were significantly increased on days 15 and 22 in AA rats, without affecting the plasma osmolality and sodium. Although CRH mRNA levels in the PVN were significantly decreased, eGFP mRNA levels in the PVN and the SON were significantly increased on days 15 and 22 in AA rats. The eGFP fluorescence in the SON, the PVN, internal and external layers of the ME and PP was apparently increased in AA compared to control rats. These results suggest that the increases in the concentrations of ACTH and corticosterone in AA rats are induced by hypothalamic AVP, based on data from AVP-eGFP transgenic rats.

Topics: Adjuvants, Immunologic; Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Arthritis, Experimental; Body Weight; Corticosterone; Drinking; Gene Expression Regulation; Green Fluorescent Proteins; Hypothalamus; Male; Osmolar Concentration; Oxytocin; Rats; Rats, Transgenic; Rats, Wistar; Recombinant Fusion Proteins; Sodium; Urinary Tract Physiological Phenomena

Oxytocin (Oxt) is secreted both peripherally and centrally and is involved in several functions including parturition, milk let-down reflex, social behavior, and food intake. Recently, it has been shown that mice deficient in Oxt receptor develop late-onset obesity. In this study, we characterized a murin model deficient in Oxt peptide (Oxt(-/-)) to evaluate food intake and body weight, glucose tolerance and insulin tolerance, leptin and adrenaline levels. We found that Oxt(-/-) mice develop late-onset obesity and hyperleptinemia without any alterations in food intake in addition to having a decreased insulin sensitivity and glucose intolerance. The lack of Oxt in our murin model also results in lower adrenalin levels which led us to hypothesize that the metabolic changes observed are associated with a decreased sympathetic nervous tone. It has been shown that Oxt neurons in the paraventricular nucleus (PVN) are a component of a leptin-sensitive signaling circuit between the hypothalamus and caudal brain stem for the regulation of food intake and energy homeostasis. Nevertheless, the lack of Oxt in these mice does not have a direct impact on feeding behavior whose regulation is probably dependent on the complex interplay of several factors. The lack of hyperphagia evident in the Oxt(-/-) mice may, in part, be attributed to the developmental compensation of other satiety factors such as cholecystokinin or bombesin-related peptides which merits further investigation. These findings identify Oxt as an important central regulator of energy homeostasis.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Brain Stem; Crosses, Genetic; Energy Intake; Glucose Intolerance; Hypothalamus; Insulin; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Oxytocin; Signal Transduction; Stomach; Sympathetic Nervous System

The object of work is pointing out the significance of improvement highly risk pregnancies by applying artificial fetal lungs maturation in relation to expected outcomes without adequate therapy.. We analyzed fetal lung maturation by using lecithin and sphingomyelin ratio in embryo fluid received by foam test. We examined successfulness of artificial fetal lungs maturation by applying corticosteroids to the embryo in a group of patients with serious form of growth retardation (group A), then to the mother (group B) and by inducing partial mild form of asphyxia with oxytocin infusion (group C).. The success of the method is shown by the success of finished pregnancies. We followed the difference between expected and actual term of delivery.. Artificial fetal lungs maturation by applying fetal corticosteroids efficiently increases the creation of lecithin and sphingomyelin and enables life of neonate even in period up to 30th week of gestation.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Amniotic Fluid; Apgar Score; Body Weight; Female; Fetal Growth Retardation; Fetal Organ Maturity; Gestational Age; Humans; Infant, Newborn; Lecithins; Lung; Oxytocics; Oxytocin; Pregnancy; Prenatal Diagnosis; Sphingomyelins

Positive social interactions and social support may protect against various forms of mental and physical illness, although the mechanisms for these effects are not well identified. The socially monogamous prairie vole, which--like humans--forms social bonds and displays high levels of parasympathetic activity, has provided a useful model for investigating neurobiological systems that mediate the consequences of sociality. In the present study, adult female prairie voles were exposed to social isolation or continued pairing with a female sibling (control conditions) for 4 weeks. During weeks 3 and 4 of this period, animals were administered oxytocin (20 microg/50 microl, s.c.) or saline vehicle (50 microl, s.c.) daily for a total of 14 days. In Experiment 1, autonomic parameters were recorded during and following isolation or pairing. Isolation (vs. pairing) significantly increased basal heart rate (HR) and reduced HR variability and vagal regulation of the heart; these changes in isolated animals were prevented with oxytocin administration. In Experiment 2, behaviors relevant to depression [sucrose intake and swimming in the forced swim test (FST)] were measured as a function of isolation. Isolation reduced sucrose intake and increased immobility in the FST; these behaviors also were prevented by oxytocin. Administration of oxytocin did not significantly alter cardiac, autonomic or behavioral responses of paired animals. These findings support the hypothesis that oxytocinergic mechanisms can protect against behavioral and cardiac dysfunction in response to chronic social stressors, and can provide insight into social influences on behavior and autonomic function in humans.

Topics: Animals; Arvicolinae; Autonomic Nervous System; Behavior, Animal; Body Weight; Female; Heart; Heart Rate; Helplessness, Learned; Organ Size; Oxytocin; Social Isolation; Time Factors

In response to nutrient stimuli, the mediobasal hypothalamus (MBH) drives multiple neuroendocrine and behavioral mechanisms to regulate energy balance. While central leucine reduces food intake and body weight, the specific neuroanatomical sites of leucine sensing, downstream neural substrates, and neurochemical effectors involved in this regulation remain largely unknown. Here we demonstrate that MBH leucine engages a neural energy regulatory circuit by stimulating POMC (proopiomelanocortin) neurons of the MBH, oxytocin neurons of the paraventricular hypothalamus, and neurons within the brainstem nucleus of the solitary tract to acutely suppress food intake by reducing meal size. We identify central p70 S6 kinase and Erk1/2 pathways as intracellular effectors required for this response. Activation of endogenous leucine intracellular metabolism produced longer-term reductions in meal number. Our data identify a novel, specific hypothalamus-brainstem circuit that links amino acid availability and nutrient sensing to the control of food intake.

Topics: Animals; Anorexia; Body Weight; Bone Morphogenetic Protein Receptors, Type I; Brain Stem; Butadienes; Dose-Response Relationship, Drug; Drug Administration Schedule; Eating; Enzyme Inhibitors; Feeding Behavior; Green Fluorescent Proteins; Hypothalamus; In Vitro Techniques; Injections, Intraventricular; Keto Acids; Leucine; Male; Melanocortins; Melanocyte-Stimulating Hormones; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural Pathways; Neurons; Nitriles; Oxytocin; Pro-Opiomelanocortin; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Signal Transduction; Threonine; Time Factors; Tyrosine; Vasotocin

Understanding the early factors affecting obesity development in males and females may help to prevent obesity and may lead to the discovery of more effective treatments for those already obese. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of obesity is characterized by hyperphagia-induced obesity, due to a spontaneous lack of CCK(1) receptors. In the present study, we focused on the behavioral and physiological aspects of obesity development from weaning to adulthood. We examined body weight, feeding efficiency, fat pad [brown, retroperitoneal, inguinal and epydidimal (in males)] weight, inguinal adipocyte size and number, leptin and oxytocin levels, body mass index, waist circumference, and females' estrous cycle structure. In the males, central hypothalamic gene expression was also examined. OLETF rats presented overall higher fat and leptin levels, larger adipocytes, and increased waist circumference and BMI from weaning until adulthood, compared with controls. Analysis of developmental patterns of gene expression for hypothalamic neuropeptides revealed peptide-specific patterns that may underlie or be a consequence of the obesity development. Analysis of the developmental trajectories toward obesity within the OLETF strain revealed that OLETF females developed obesity in a more gradual manner than the males, presenting delayed obesity-related "turning points," with reduced adipocyte size but larger postweaning fat pads and increased adipocyte hyperplasia compared with the males. Intake decrease in estrus vs. proestrus was significantly less in OLETF vs. Long-Evans Tokushima Otsuka females. The findings highlight the importance of using different sex-appropriate approaches to increase the efficacy of therapeutic interventions in the treatment and prevention of chronic early-onset obesity.

Topics: Adipocytes; Adipose Tissue; Age Factors; Aging; Animals; Blood Glucose; Body Mass Index; Body Weight; Chronic Disease; Disease Models, Animal; Disease Progression; Eating; Estrus; Feeding Behavior; Female; Gene Expression Regulation, Developmental; Hyperphagia; Hypothalamus; Leptin; Male; Neuropeptides; Obesity; Oxytocin; Rats; Rats, Inbred OLETF; Receptor, Cholecystokinin A; RNA, Messenger

Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH) was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal.. Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin.. We conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism.

Topics: Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Analysis of Variance; Animals; Body Weight; Diet; Eating; Energy Intake; Fat Emulsions, Intravenous; Feeding Behavior; Hypothalamus; In Situ Hybridization; Leucine; Male; Mice; Mice, Inbred C57BL; Mixed Function Oxygenases; Neurons; Organ Culture Techniques; Oxo-Acid-Lyases; Oxytocin; Proto-Oncogene Proteins c-fos; Reverse Transcriptase Polymerase Chain Reaction; Reward; RNA, Messenger; Sucrose

Postnatal oxytocin treatment decreases blood pressure and increases body weight in adult normotensive rats. The aim of the present study was to investigate the effect of postnatally administered oxytocin on blood pressure, heart rate and body weight in spontaneously hypertensive rats (SHR). For this purpose SHR male pups were given oxytocin (1 mg/kg) or saline subcutaneously once a day on days 10-14 after birth. Blood pressure and heart rate were measured at the age of 2 months. Weight was registered continuously. The postnatally oxytocin-treated male SHR had significantly lower systolic blood pressure as adults compared to the controls (158 vs. 169; p<0.05). They also had a tendency to lower diastolic blood pressure (119 vs. 128; p=0.10). Heart rate was equal in the two groups. The postnatally oxytocin-treated male SHR had a significantly lower body weight at the age of 5-8 weeks compared to the controls (ANOVA p=0.014).

Topics: Analysis of Variance; Animals; Blood Pressure; Body Weight; Heart Rate; Injections, Subcutaneous; Male; Oxytocin; Rats; Rats, Inbred SHR; Time Factors

Adaptive changes in serotonin2A (5-HT(2A)) receptor signaling are associated with the clinical response to a number of psychiatric drugs including atypical antipsychotics and selective serotonin reuptake inhibitors. The present study examined possible mechanisms of agonist-induced desensitization of 5-HT(2A) receptors in rat hypothalamic paraventricular nucleus (PVN) after 4 and 7 days of treatment with 1mg/kg (-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). The magnitude of 5-HT(2A) receptor-mediated oxytocin release decreased 78% after 4 days and 61% after 7 days of DOI treatment. Similarly, the magnitude of ACTH release following 1mg/kg DOI decreased by 31% after 4 days and 38% after 7 days of DOI treatment. Treatment with DOI for either 4 or 7 days caused a significant decrease (by approximately 50%) in the high-affinity 5-HT(2A) receptor binding as measured by (125)I-DOI binding compared to saline-treated control rats. In contrast, western blot analysis demonstrated a significant increase in 5-HT(2A) receptor protein levels with 4 or 7 days of DOI treatment to 167% and 191% of control levels, respectively. Real time quantitative RT-PCR analysis revealed a small but nonsignificant increase in the levels of 5-HT(2A) mRNA following treatment with DOI for 4 or 7 days. Taken together, the 5-HT(2A) receptor-stimulated hormone responses, agonist binding data and western blot data suggest that although agonist treatment increases the levels of 5-HT(2A) receptor protein in the cell membrane, there is a reduction in the population of 5-HT(2A) receptors capable of high-affinity binding and mediating a functional response.

Topics: Adrenocorticotropic Hormone; Amphetamines; Analysis of Variance; Animals; Autoradiography; Body Weight; Dose-Response Relationship, Drug; Drug Administration Schedule; Gene Expression Regulation; Iodine Isotopes; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Protein Binding; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; RNA, Messenger; Serotonin Receptor Agonists; Time Factors

The present study was performed to elucidate whether mesotocin (MT), one of avian neurohypophysial hormones, relates to the action of arginine vasotocin (AVT) on oviposition of hens. The ratio of AVT-induced oviposition was increased when 1 microg/hen of MT was injected together with AVT. An intravenous injection of 1 microg/hen of MT caused an increase in the binding affinity of the uterine AVT receptor and a decrease in the binding capacity. Blood MT concentrations measured by RIA increased approximately 1 min before oviposition during the period of the bearing-down behavior, but the AVT concentration did not change at this time. The blood AVT concentration dramatically increased within 1 min just after oviposition. The results suggest that MT may have an effect of enhancing the inducing oviposition by AVT through the increase in the sensitivity of the uterus to AVT at oviposition in hens.

Topics: Animals; Body Weight; Chickens; Female; Oviducts; Oviposition; Oxytocin; Receptors, Vasopressin; Uterus; Vasotocin

Chronic subordinate colony (CSC) housing has recently been shown to be a clinically relevant model of chronic psychosocial stress for male mice and to cause an increase in the animals' anxiety-related behavior on the plus-maze. Here, we investigated (1) the detailed subordinate/dominant behavior during CSC housing, (2) the anxiety-related behavior of CSC and control mice in two independent tests, and (3) whether CSC exposure also influences the hypothalamic expression of oxytocin (OXT) and/or arginine vasopressin (AVP), specifically within the paraventricular nucleus. Both neuropeptides are known to be involved in the regulation of anxiety and stress responses. Behavioral observation revealed that all male CSC mice that were co-housed with a slightly larger male mouse obtained a subordinate status within their colonies over 19 consecutive days. Furthermore, CSC exposure resulted in diminished body weight gain and increased anxiety-related behavior as quantified both on the elevated plus-maze and in the light-dark box. Hypothalamic mRNA levels of OXT remained unchanged, whereas AVP mRNA was found to be decreased on day 20 of CSC exposure. In conclusion, exposure to CSC enhances anxiety, an effect that seems to be independent of the hypothalamic expression of the neuropeptides OXT and AVP.

Topics: Animals; Anxiety; Arginine Vasopressin; Behavior, Animal; Body Weight; Housing, Animal; Hypothalamus; Male; Mice; Mice, Inbred C57BL; Neuropsychological Tests; Oxytocin; Random Allocation; Social Behavior; Stress, Psychological

Single-minded 1 (Sim1) encodes a transcription factor essential for formation of the hypothalamic paraventricular nucleus (PVN). Sim1 haploinsufficiency is associated with hyperphagic obesity and increased linear growth in humans and mice, similar to the phenotype of melanocortin 4 receptor (Mc4r) mutations. PVN neurons in Sim1(+/-) mice are hyporesponsive to the melanocortin agonist melanotan II. PVN neuropeptides oxytocin (Oxt), TRH and CRH inhibit feeding when administered centrally. Consequently, we hypothesized that altered PVN neuropeptide expression mediates the hyperphagia of Sim1(+/-) mice. To test this hypothesis, we measured hypothalamic expression of PVN neuropeptides in Sim1(+/-) and wild-type mice. Oxt mRNA and peptide were decreased by 80% in Sim1(+/-) mice, whereas TRH, CRH, arginine vasopressin (Avp), and somatostatin mRNAs were decreased by 20-40%. Sim1(+/-) mice also showed abnormal regulation of Oxt but not CRH mRNA in response to feeding state. A selective Mc4r agonist activated PVN Oxt neurons in wild-type mice, supporting involvement of these neurons in melanocortin feeding circuits. To test whether Oxt itself regulates feeding, we measured the effects of central administration of an Oxt receptor antagonist or repeated doses of Oxt on food intake of Sim1(+/-) and wild-type mice. Sim1(+/-) mice were hypersensitive to the orexigenic effect of the Oxt receptor antagonist. Oxt decreased the food intake and weight gain of Sim1(+/-) mice at a dose that did not affect wild-type mice. Our results support the importance of Oxt neurons in feeding regulation and suggest that reduced Oxt neuropeptide is one mechanism mediating the hyperphagic obesity of Sim1(+/-) mice.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Body Weight; Hyperphagia; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Biological; Mutation; Neurons; Neuropeptides; Obesity; Oxytocin; Phenotype; Receptor, Melanocortin, Type 4; Repressor Proteins

To understand the adaptation to lactation of obese rats, by studying the interplay among the gut hormone cholecystokinin (CCK), the adiposity hormone leptin and the affiliation hormone oxytocin in modulating body mass and fat storage.. Strain differences were examined between Otsuka Long Evans Tokushima Fatty (OLETF) rats lacking expression of functional CCK-1 receptors and Long Evans Tokushima Otsuka (LETO) controls, tested as nulliparous dams, at the 7 and 15th lactation day, at weaning (lactation day 22) or 8 weeks postweaning.. We measured body mass, fat pads (brown, retroperitoneal and inguinal) and inguinal adipocytes. Plasma levels of leptin and oxytocin were determined.. Fat depots of LETO female rats were larger during lactation compared to the levels found in postweaning and nulliparous female rats. LETO female rats gained weight and accumulated fat during pregnancy and lactation, returning to their normal fat levels postweaning. In contrast, OLETF female rats presented lower body weight and fat depots during the lactation period than nulliparous dams, and regained the weight and fat postweaning. Plasma leptin and oxytocin were highly correlated and followed the same pattern. OLETF leptin levels were highly correlated with fat depot and inguinal cell surface. No significant correlation was found for LETO parameters.. Pregnancy and lactation are energy-consuming events, which naturally induce female rats to increase food intake and accumulate fat. When challenged by the demands of rapidly growing preobese OLETF pups, OLETF dams' fat stores are reduced to lean, LETO levels. During lactation, sensitivity of the oxytocinergic neurons descending from the paraventricular nuclei to the nucleus of the solitary tract to CCK is reduced. We theorized that this pathway is not available to OLETF female rats that lack functional CCK-1 receptors to mediate the signal. The current study contributes to the understanding of the female body's adaptation to lactation.

Topics: Adaptation, Physiological; Adipocytes; Adipose Tissue; Animals; Body Weight; Disease Models, Animal; Female; Hypertrophy; Lactation; Leptin; Mutation; Obesity; Oxytocin; Rats; Rats, Inbred OLETF; Receptors, Cholecystokinin; Weaning; Weight Gain

We analyzed temperature homeostasis in oxytocin-deficient (Oxt(-/-)) mice and found that Oxt(-/-) mice exhibited lower body temperatures than wild-type animals when they were exposed to cold. Oxt(-/-) mice also showed slightly more weight gain, but there were no obvious differences in the morphology of white and brown adipose tissues as between wild-type and Oxt(-/-) mice. In cold-exposed conditions, oxytocin neurons containing c-Fos immunoreactivity existed in the paraventricular nucleus of the hypothalamus. These results suggest that the central oxytocin neurons constitute part of the thermoregulatory system involved in maintaining body temperature in cold environments.

Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Body Temperature Regulation; Body Weight; Cold Temperature; Mice; Mice, Knockout; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos

Our purposes were to determine the effect of preeclampsia, magnesium sulfate prophylaxis, and maternal weight on labor induction in women with preeclampsia and identify risk factors associated with its failure.. Fifty-five preeclamptic women and 176 non-preeclamptic women requiring labor induction over an 18-month period were studied retrospectively. Prostaglandin E(2) (dinoprostone) and oxytocin were used for labor induction. Women with rupture of the membranes, spontaneous contraction resulting in cervical change, or an initial cervical examination showing more than 2 cm dilatation and 50% effacement were excluded. Statistics were analyzed with chi(2) test, Fisher's exact test, Student t test, Mann-Whitney U test, and multiple logistic regression.. The women with preeclampsia had a significantly higher rate of failed induction than did those without preeclampsia (p = 0.01). However, the women with preeclampsia had a higher mean maternal weight and an increased use of magnesium sulfate, and labor was induced at earlier gestational age than in those without preeclampsia (p < 0.05 for each). Multiple logistic regression showed that the use of magnesium sulfate, higher maternal weight, and unfavorable cervix, but not preeclampsia, were significantly associated with an increased risk of failed induction after correction for known confounding variables.. Although the risk of failed induction is increased in preeclamptic women, preeclampsia is not an independent risk factor for failed induction. The use of magnesium sulfate, higher maternal weight, and unfavorable cervix are independent risk factors for failed induction.

Topics: Adult; Anticonvulsants; Body Weight; Case-Control Studies; Chi-Square Distribution; Dinoprostone; Female; Humans; Labor, Induced; Magnesium Sulfate; Oxytocin; Pre-Eclampsia; Pregnancy; Retrospective Studies; Seizures

Regulation of vasopressin (VP) and oxytocin (OT) secretion involves integration of neural signals from hypothalamic osmoreceptors, ascending catecholaminergic and peptidergic cell groups in the brain stem, and local and autoregulatory afferents. Neuropeptide Y (NPY) is one factor that stimulates the release of VP and OT from the supraoptic (SON) and paraventricular nuclei of the hypothalamus via activation of Y1 receptors (Y1R). The current studies were designed to assess the regulation and distribution of NPY Y1R expression in the SON of male rats that were either given 2% NaCl drinking water (24-72 h) or water deprived (48 h). Subjecting male rats to these conditions resulted in significant increases in both the number of cells expressing Y1R immunoreactivity (ir) and the amount of Y1R protein per cell within the SON. Y1R immunoreactivity was increased in the magnocellular but not medial parvocellular paraventricular nuclei, and Y1R mRNA levels were increased in the SON of salt-loaded rats. Subpopulations of both VP and OT cells in the hypothalamus express Y1R immunoreactivity and a greater percentage of VP-ir cells express Y1R after salt loading. To control for potential effects of dehydration-induced anorexia, a group of euhydrate animals was pair fed with animals consuming 2% NaCl. No detectable change in Y1R expression was observed in the SON of pair-fed animals, even though body weights were significantly lower than controls. These data demonstrate that NPY Y1R gene and protein expression are increased in the SON of salt-loaded and water-deprived animals and provide a mechanism whereby NPY can support VP/OT release during prolonged challenges to fluid homeostasis.

Topics: Animals; Blood; Body Weight; Dehydration; Gene Expression; Hypothalamus; Immunohistochemistry; Male; Neurons; Osmolar Concentration; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Sodium Chloride; Supraoptic Nucleus; Vasopressins; Water Deprivation

Under certain circumstances, central oxytocin (OT) pathways inhibit dietary intake of NaCl in rats and mice. C57BL/6 OT knockout (OT KO) mice were reported to consume greater amounts of saline solution than wild type (WT) cohorts when both were water deprived overnight. In this study, we determined that OT KO and WT mice of C57BL/6 strain demonstrate an equivalent taste aversion for continuously available 0.2 M, 0.3 M or 0.5 M NaCl. The aversion was proportional to the concentration of NaCl, similar to what has been reported in rats. Furthermore, OT KO and WT animals ingested the same daily amounts of a low, 0.01%, regular, 1.0%, and a high, 8.0%, NaCl diet that was provided ad libitum as a single choice. While consuming these diets, mice were given the choice to drink water or saline (0.5 M NaCl). As the amount of NaCl in the diet increased, mice of both genotypes significantly decreased the consumption of saline solution to an equal degree. Additionally, in an experimental model of sustained dehydration previously developed in rats, 0.5 M NaCl was the only available drinking fluid. Like rats subjected to this paradigm, OT KO and WT mice decreased food intake, decreased body weight and increased fluid ingestion with no genotypic differences. These findings suggest that oxytocinergic neuronal pathways cannot be the only regulator of ad libitum intake of NaCl in drinking solutions or diet. It appears that OT pathways may be more critical in controlling NaCl intake over brief intervals when an animal is quickly compensating for a dehydrating stimulus.

Topics: Analysis of Variance; Animals; Behavior, Animal; Body Weight; Drinking; Drinking Behavior; Eating; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxytocin; Sodium; Sodium, Dietary; Time Factors

In the present study the effects of oxytocin administered subcutaneously (s.c.) or intravaginally (i.vag.) on spontaneous motor activity, nociceptive thresholds and plasma corticosterone levels were examined in female ovariectomized (OVX) rats.. Oxytocin (1 mg/kg s.c. or 100 microg i.vag.) was administered once a day for 10 days to OVX rats. Controls received saline s.c. or cellulose gel i.vag. Spontaneous motor activity was observed in an open-field arena, nociceptive thresholds were investigated by the tail-flick test, and corticosterone and oxytocin plasma levels were measured by radioimmunassay, 3, 4 and 5 days respectively, after the end of the treatment period.. Both oxytocin administered s.c. and i.vag. increased forward locomotion (p<0.05) and nociceptive thresholds (p<0.05) significantly. In addition, oxytocin s.c. increased the amount of locomotor activity (p<0.05). Plasma corticosterone levels were decreased (p<0.05) and oxytocin levels were unchanged when measured 5 days after the last administration of oxytocin s.c. or i.vag.. The present data indicate that oxytocin induces a spectrum of long-lasting effects in OVX rats, including an increase in spontaneous motor activity, elevation of nociceptive thresholds and decrease of corticosterone levels. Similar effects may be induced by estrogens. In addition, these data indicate that i.vag. administration of oxytocin may be used to induce oxytocin-mediated effects.

Topics: Administration, Intravaginal; Analysis of Variance; Animals; Body Weight; Corticosterone; Female; Injections, Subcutaneous; Motor Activity; Nociceptors; Ovariectomy; Oxytocics; Oxytocin; Pain Measurement; Rats; Rats, Sprague-Dawley

Various childhood mood disorders are being treated with serotonin selective reuptake inhibitors (SSRIs) such as fluoxetine (Prozac(R)), yet limited data are available on their effects on serotonergic systems prior to maturation. This study investigated the effects of chronic fluoxetine treatment on 5-HT2A serotonin receptor-mediated neuroendocrine responses in young male rats. Prepubescent male rats were treated with saline or fluoxetine (10 mg/kg/day, i.p.) for 14 days, a treatment regimen producing maximal changes in postsynaptic 5-HT2A function in adults. Eighteen hours post-treatment, the rats received saline or increasing doses (0.5, 2.0, or 5.0 mg/kg, i.p.) of the 5-HT2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl ((+/-)-DOI). Trunk blood was obtained to determine changes in oxytocin, ACTH, corticosterone, and renin responses. Fluoxetine produced a small ( approximately 6%) but significant reduction in body weight gain, but no changes were observed in basal hormone levels. In both saline- and fluoxetine-treated rats, (+/-)-DOI increased plasma oxytocin levels in a dose-dependent manner. However, the magnitude of the oxytocin responses to all doses of (+/-)-DOI were markedly attenuated ( approximately 50%) in the fluoxetine-treated rats, indicating a functional reduction in the E(max) of 5-HT(2A) receptor-mediated oxytocin responses. In contrast, fluoxetine did not alter the (+/-)-DOI-induced increases in plasma ACTH, corticosterone, or renin. These data provide the first demonstration of selective neuroadaptive responses in 55-HT2A serotonin receptor function due to prepubescent treatment with fluoxetine. These data may be clinically relevant with respect to the use of selective serotonin reuptake inhibitors in children and adolescents.

Topics: Adrenocorticotropic Hormone; Aging; Animals; Body Weight; Brain; Corticosterone; Dose-Response Relationship, Drug; Fluoxetine; Hypothalamo-Hypophyseal System; Male; Neurosecretory Systems; Oxytocin; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Renin; Reproduction; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Up-Regulation

The link between impaired maternal behavior (MB) and cocaine treatment could result from drug-induced decreases in maternal reactivity to offspring, prenatal drug exposure (PDE) in offspring that could alter their ability to elicit MB, or the interaction of both, which could subsequently impair MB of the 1st-generation dams. Following chronic or intermittent cocaine or saline treatment during gestation, rat dams rearing natural or cross-fostered litters were compared along with untreated dams for MB. Untreated 1st-generation females with differentially treated rearing dams and PDE were tested for MB with their natural litters. The authors report disruptions in MB in dams and their 1st-generation offspring, attributable to main and interaction effects of maternal treatment, litter PDE, and rearing experience.

Topics: Age Factors; Analysis of Variance; Anesthetics, Local; Animals; Animals, Newborn; Behavior, Animal; Body Weight; Brain; Cocaine; Exploratory Behavior; Female; Intergenerational Relations; Male; Maternal Behavior; Oxytocin; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Rats; Rats, Sprague-Dawley; Reaction Time

Tryptophan depleting protocols are commonly used to study the role of serotonin in mood disorders. The present study examined the impact of a tryptophan-deficient diet and fluoxetine on the serotonergic regulation of neuroendocrine function and body weight. We hypothesized that the regulation of postsynaptic 5-HT1A receptors is dependent on the levels of 5-HT in the synapse. Rats on a control or a tryptophan-deficient diet received daily injections of saline or fluoxetine (5 or 10 mg.kg-1.day-1 ip) from day 7 to day 21. The tryptophan-deficient diet produced a 41% reduction in the level of 5-HT but no change in the density of [3H]paroxetine-labeled 5-HT transporters. Treatment with fluoxetine inhibited the gain in weight in rats maintained on the control diet. The tryptophan-deficient diet produced a significant loss in body weight that was not significantly altered by treatment with fluoxetine. Treatment with fluoxetine produced a dose-dependent desensitization of hormone responses to injection of the 5-HT1A receptor agonist (+/-)8-hydroxy-2-(di-n-propylamino)tetralin ((+/-)8-OH-DPAT). The tryptophan-deficient diet produced an increase in the basal levels of corticosterone but did not alter the basal levels of ACTH or oxytocin. Also, this diet inhibited the magnitude of 8-OH-DPAT-induced increase in plasma levels of ACTH and oxytocin but did not impair the ability of fluoxetine to desensitize the 5-HT1A receptor-mediated increase in plasma hormones. These data suggest that a reserve of 5-HT enables fluoxetine to desensitize postsynaptic 5-HT1A receptors in the hypothalamus. In conclusion, the profound physiological changes induced by tryptophan depletion may complicate the interpretation of studies using this experimental approach.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Adrenocorticotropic Hormone; Animals; Body Weight; Brain; Corticosterone; Diet; Fluoxetine; Hormones; Male; Neurosecretory Systems; Oxytocin; Rats; Rats, Sprague-Dawley; Receptors, Serotonin, 5-HT1; Selective Serotonin Reuptake Inhibitors; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Tryptophan

In the present study, diurnal changes in plasma levels of melatonin and cortisol, and hypothalamic contents of neurohypophysial hormone mRNAs were examined in pre-spawning chum salmon, Oncorhynchus keta. From late November to early December, homing fish were captured at two sites along their migratory pathway on the Sanriku coast, Japan. Fish captured in the seawater (SW) environment were transferred to SW aquaria, and fish captured in the freshwater (FW) environment were to FW aquaria. They were maintained under natural photoperiod of approximately 10L:14D and sacrificed at 4-h interval through 24-h period. Plasma levels of melatonin were determined by radioimmunoassay, while cortisol levels were determined by enzyme immunoassay. Hypothalamic contents of vasotocin and isotocin mRNAs were determined by quantitative dot-blot hybridization assay. The melatonin levels showed weak nocturnal elevations in the SW and FW males, and FW females. The levels were maximal at 22:00 and minimal at 10:00 or 14:00, however the amplitudes were smaller than those reported in the previous studies using immature salmonids. The levels of vasotocin and isotocin mRNAs were higher in the males at all time points. The mRNA levels, however, did not show any diurnal variations in either of group. The same applied to plasma cortisol levels. These results indicate that the diurnal endocrine rhythms were attenuated in pre-spawning chum salmon, in contrast to the prominent diurnal rhythms in immature salmonids.

Topics: Animals; Body Weight; Circadian Rhythm; Female; Hydrocortisone; Hydroxyprogesterones; Hypothalamus; In Situ Hybridization; Male; Melatonin; Oncorhynchus keta; Oxytocin; Radioimmunoassay; RNA, Messenger; Vasotocin

Oxytocin (OT) modulates adult mammalian sexual behavior, sperm production and transport, and steroidogenesis; however, the consequences of developmental manipulations of oxytocin have received little attention. The purpose of this experiment was to determine whether neonatal exposure to OT, an oxytocin antagonist (OTA), saline (SAL), or handling (HAN)-only would have long-term effects on reproductive potential in male prairie voles (Microtus ochrogaster). Adult males were observed for 24 h with a sexually receptive female and sexual behavior was recorded. Females were subsequently lavaged and smears were examined for sperm. Reproductive parameters including motility of epididymal sperm, testis weight, and plasma androgen levels were in the normal range. OT-treated males that did not mate within the first 30 min did not mate at all, and in comparison to controls, a higher proportion of those OT-treated and OTA-treated males that did mate did not transfer sperm to the females. OTA-treated males also had significantly higher testicular sperm concentrations than HAN-only males, and significantly lower epididymal sperm concentrations. These differences suggest that in males, developmental manipulations of OT may have the potential to influence the subsequent expression of sexual behavior and sperm transport.

Topics: Androgens; Animals; Animals, Newborn; Arvicolinae; Body Weight; Epididymis; Female; Male; Organ Size; Oxytocin; Pair Bond; Reproduction; Sexual Behavior, Animal; Social Behavior; Sperm Motility; Testis

The purpose of this cross-fostering study was to investigate neonatal survival following exposure of pregnant rats to atosiban (1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin), an oxytocin antagonist. Atosiban was administered subcutaneously from days 15 to 20 of gestation at 300 mg/kg/day, and controls received vehicle alone. Parturition was observed at 30 min intervals throughout the period that births were occurring. There was no effect of treatment on number of pups born or neonatal viability. Within 1 h of birth, litter size was standardised to five males and five females, followed immediately by cross-fostering either between or within groups. Offspring from treated mothers reared by control mothers had normal survival and weight gain. There was poor survival and weight gain in offspring from control mothers reared by treated mothers. There was clear evidence that lactation was impaired in the treated females, leading to the conclusion that poor neonatal survival in offspring reared by treated mothers was attributable to a failure of milk let-down.

Topics: Animals; Animals, Newborn; Body Weight; Female; Hormone Antagonists; Injections, Subcutaneous; Litter Size; Longevity; Male; Maternal-Fetal Exchange; Milk Ejection; Oxytocin; Parturition; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Vasotocin; Weight Gain

In the present study, we localized oxytocin (OT) and its receptor (OTR) in the rat aorta, and investigated whether genistein, an isoflavonic phytoestrogen, influences their expression in ovariectomized (OVX) rats deficient in estrogen.. OVX Sprague-Dawley rats were randomized to the following groups: genistein (from 0.02 to 5 microg/g/day, s.c. for 10 days), estradiol (E(2,) 0.1 microg/g/day, s.c. for 10 days) or their respective vehicles. OT and OTR immunostaining was concentrated in the aortic tunica intima, suggesting their paracrine/autocrine action within endothelial cells. Reverse transcription-polymerase chain reaction analysis showed that 1 and 5 microg/g but not 0.1 microg/g genistein elevated OT mRNA (2-fold P<0.05), OTR mRNA (2.5-fold, P<0.05) and endothelial nitric oxide synthase (eNOS) mRNA (2-fold, P<0.05) in the aorta of OVX rats. In addition, genistein treatment increased estrogen receptor alpha (ERalpha) (2- to 3-fold, P<0.05) but resulted in a 50% decrease of ERbeta (P<0.05). These genistein effects were neutralized by treatment of OVX rats with the ER antagonist ICI 182,780 (1.5 microg/g/day, s.c. for 10 days). Similarly, Western blot analysis revealed an increase of 67-kDa OTR, 140-kDa eNOS, 62-kDa ERalpha and a decrease of 55-kDa ERbeta (P<0.05) in the aorta of OVX rats treated with genistein. In contrast, the treatment of OVX rats with E(2) elevated ERbeta mRNA (1.5 fold, P<0.05) but similarly to genistein increased OT, OTR, eNOS and ERalpha mRNA.. These results provide the first evidence of OT and OTR co-localization in endothelial cells. The response to genistein via ER activation can be regarded as a recovery from endothelial dysfunction induced by ovariectomy.

Topics: Animals; Aorta; Body Weight; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Genistein; Growth Inhibitors; Immunohistochemistry; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Organ Size; Ovariectomy; Oxytocin; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Receptors, Oxytocin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stimulation, Chemical; Tunica Intima; Uterus

Repeated oxytocin administration to adult rats causes a long-term decrease of plasma levels of corticosterone and blood pressure and stimulates growth and fat retention. Maternal undernutrition increases blood pressure and plasma corticosterone in adult offspring. We hypothesized that oxytocin treatment early in life would alleviate adverse effects of intrauterine food restriction. Male pups from ad libitum-fed and food-restricted (fed 60% of ad libitum intake) dams were injected with oxytocin or saline in days 1-14 after birth. At 4 mo, blood pressure, plasma levels of corticosterone, and adiposity were assessed. Oxytocin treatment decreased blood pressure independently of nutrition, whereas the increased plasma levels of corticosterone were lowered to normal levels in food-restricted offspring. Blood pressure and adiposity were not affected by in utero food restriction, whereas birth and adult weight were. In conclusion, postnatal events may alleviate adverse effects caused by in utero food restriction. In contrast to more severe food restriction, a moderate general food restriction during gestation had no effect on blood pressure in the offspring.

Topics: Aging; Animals; Animals, Newborn; Birth Weight; Blood Pressure; Body Weight; Corticosterone; Female; Food Deprivation; Heart Rate; Male; Nutrition Disorders; Oxytocin; Pregnancy; Pregnancy Complications; Rats; Rats, Sprague-Dawley

Differential adaptive changes in serotonin2A [5-hydroxytryptamine (5-HT)2A] receptor signaling during treatment may be one mechanism involved in the latency of therapeutic improvement with antidepressants, such as fluoxetine. We examined the effects of fluoxetine (2, 3, 7, 21, or 42 days) on hypothalamic 5-HT2A receptor signaling. The hormone responses to an injection of the 5-HT2A receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane HCl (DOI) were used as an index of hypothalamic 5-HT2A receptor function. Treatment with fluoxetine for 21 or 42 days produced diminished adrenocorticotropic hormone (ACTH) and oxytocin (but not corticosterone) responses to DOI injections (2.5 mg/kg i.p.; 15 min postinjection). Regulators of G protein signaling 4 and Galphaq protein levels in the hypothalamic paraventricular nucleus were not altered during fluoxetine treatment. Because previous studies indicate that treatment with fluoxetine for 21 days resulted in increased hormone responses to DOI when measured at 30 min after injection, we examined the effect of fluoxetine (21 days) on DOI-induced increase hormone levels at 15, 30, and 60 min after DOI injection. Fluoxetine decreased the oxytocin response at 15 but not at 30 min post-DOI injection, and potentiated the ACTH and corticosterone responses at 30 min post-DOI injection. For comparison, we examined the effect of fluoxetine on 5-HT2A receptor-mediated increase in phospholipase C (PLC) activity in the frontal cortex. 5-HT-stimulated, but not guanosine 5'-O-(3-thio)triphosphate-stimulated PLC activity was increased after 21 days of fluoxetine-treatment. Overall, these results indicate that chronic fluoxetine treatment can potentiate 5-HT2A receptor signaling in frontal cortex but differentially alters 5-HT2A receptor signaling in oxytocin-containing neurons and corticotropin-releasing factor-containing neurons in the paraventricular nucleus.

Topics: Animals; Body Weight; Corticotropin-Releasing Hormone; Fluoxetine; GTP-Binding Protein alpha Subunits, Gq-G11; Heterotrimeric GTP-Binding Proteins; Indophenol; Male; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; RGS Proteins; Selective Serotonin Reuptake Inhibitors; Signal Transduction; Time Factors; Type C Phospholipases

The vasopressin (VP) magnocellular neurosecretory cells (MNCs) in the supraoptic and paraventricular (PVN) nuclei are regulated by estrogen and exhibit robust expression of estrogen receptor (ER)-beta. In contrast, only approximately 7.5% of oxytocin (OT) MNCs express ER-beta. We examined the osmotic regulation of ER-beta mRNA expression in MNCs using quantitative in situ hybridization histochemistry. Hyper-osmolality induced via 2% hypertonic saline ingestion significantly decreased, whereas sustained hypo-osmolality induced via d-d-arginine VP and liquid diet increased ER-beta mRNA expression in MNCs (p < 0.05). Thus, the expression of ER-beta mRNA correlated inversely with changes in plasma osmolality. Because hyper-osmolality is a potent stimulus for VP and OT release, this suggests an inhibitory role for ER-beta in MNCs. Immunocytochemistry demonstrated that the decrease in ER-beta mRNA was translated into depletion of receptor protein content in hyper-osmotic animals. Numerous MNCs were positive for ER-beta in control animals, but they were virtually devoid of ER-beta-immunoreactivity (IR) in hyper-osmotic animals. The osmotically induced decrease in ER-beta expression was selective for MNCs because ER-beta-IR remained unaltered in PVN parvocellular neurons. Plasma estradiol and testosterone were not correlated with ER-beta mRNA expression after osmotic manipulation, suggesting that ER-beta expression was not driven by ligand availability. Expression of FOS-IR in MNCs with attenuated ER-beta-IR, and the absence of FOS-IR in parvocellular neurons that retain ER-beta-IR suggest a role for neuronal activation in the regulation of ER-beta expression in MNCs. Thus, osmotic modulation of ER-beta expression in MNCs may augment or attenuate an inhibitory effect of gonadal steroids on VP release.

Topics: Animals; Blood Volume; Body Weight; Estrogen Receptor beta; Hematocrit; Hormones; Hypernatremia; Hyponatremia; Male; Neurons; Osmolar Concentration; Osmotic Pressure; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Sodium Chloride; Supraoptic Nucleus; Vasopressins; Water-Electrolyte Balance; Water-Electrolyte Imbalance

There is evidence that the central oxytocin system is activated and undergoes reorganization before parturition. The present study was designed to determine the effects of central oxytocin receptor blockade during late gestation on parturition, pup growth, and oxytocin release during suckling. Female Sprague-Dawley rats were implanted on gestation day 12-14 with Alzet osmotic minipumps containing an oxytocin receptor antagonist (d(CH2)5, Tyr(Me)(2), Orn(8)-vasotocin; OT-X) or artificial cerebrospinal fluid (VEH), which was infused into the third cerebral ventricle. Pumps were removed within 24 h of parturition. Daily maternal body weight and food intake were monitored during gestation and lactation. The length of gestation, duration of parturition, pup number, litter weight and interbirth interval were recorded. Subsequently, pup number and litter weights were recorded daily until lactation day 10 or 11, when maternal and pup behaviour, and plasma oxytocin concentration before and during suckling were measured. Central oxytocin blockade had no effect on the timing of parturition, maternal behaviour, litter size, still births, or litter weights at birth. However, beginning on day 3 of lactation, average weights of litters of OT-X females were significantly lower than litters of VEH-treated females. Furthermore, while basal plasma oxytocin concentrations, oxytocin increases in response to suckling and dam/pup interactions did not differ between groups, a significant delay in suckling-induced systemic oxytocin release was observed in OT-X females. Finally, OT-X dams weighed less than VEH dams during the postpartum observation period, although food intakes were similar. These data suggest that central actions of oxytocin during late gestation are necessary for the normal timing of systemic release of oxytocin during suckling, normal pup weight gain, and maintenance of maternal body weight.

Topics: Animals; Animals, Suckling; Behavior, Animal; Body Weight; Eating; Female; Gestational Age; Lactation; Maternal Behavior; Oxytocin; Parturition; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin

Oestrogens affect fluid balance, influencing both ingestive behaviour and renal excretion. The renal effects are partly due to altered release of vasopressin and oxytocin. This study was designed to explore the role of oestrogen receptor-beta (ERbeta) in neurohypophysial hormonal function. Following dietary administration, soya isoflavones reach the brain in sufficient concentration to activate ERbeta, but not oestrogen receptor-alpha (ERalpha). ERbeta function was therefore manipulated by feeding rat diets differing in soya isoflavone content. Fluid balance and neurohypophysial hormone release were measured in male rats maintained for 14 days on a soya isoflavone-free diet or one containing 150 microg/g genistein+daidzein. Food and water intake, body weight, urine flow, osmolality and sodium concentrations were determined daily. After 14 days, plasma and urine osmolality and sodium, vasopressin and oxytocin concentrations were determined. There was no significant difference in weight gain between the two groups or in their excretion of sodium and water or plasma sodium and plasma oxytocin. However, plasma vasopressin was significantly lower in the iso-free group. Double-label immunocytochemistry was used to assess colocalisation of ERbeta with the neurohypophysial hormones in male rats. Cell nuclei showing ERbeta immunoreactivity were abundant in the posterior magnocellular paraventricular nucleus (PVNpm) and in the supraoptic nucleus (SON). Vasopressin-immunoreactive neurones were similarly distributed, forming the core of the PVNpm and the ventral portion of the SON; majority were positive for ERbeta. Cells with oxytocin immunoreactivity were located mainly at the periphery of the PVNpm and in the dorsal SON; only approximately a quarter of these cells showed ERbeta immunoreactivity. Thus, the difference in the effects of the soya diet on vasopressin and oxytocin release may be related to the ERbeta-activating properties of this diet and to the preponderance of this receptor in vasopressin as opposed to oxytocin cells.

Topics: Animals; Body Weight; Diet; Drinking; Eating; Estrogen Receptor beta; Female; Glycine max; Immunohistochemistry; Male; Osmolar Concentration; Oxytocin; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Rats; Receptors, Estrogen; RNA, Messenger; Supraoptic Nucleus; Vasopressins; Water-Electrolyte Balance

The effects of pineal peptides (mol. mass 1-4 kDa) intranasal infusions on some parameters of milk-ejection reflex were investigated. Peptides were extracted from dairy-cattle pineal glands. Pineal peptides increase body weight, levels of water intake, plasma prolactin concentration and milk yield in rats when infusing daily in dose 1 microgram/kg from the third day of lactation. On 9th and 12th days of lactation during 1-hour nursing seance the significantly greater number of reflective milk ejections were found. When 1 hour before the peptides infusion rats were intraperitoneally injected by rabbit antiserum to oxytocin (200 microliters at dilution of 1:20) the effects of pineal peptides were significantly less expressive or were absent at all. Using enzymimmunoassay it was demonstrated that there were greater increasing of oxytocin content in pineal gland in suckling-induced oxytocin release from neurohypophysial system in the chronic pineal peptides-treated female rats compared with control. This effect was absent when rats were injected by oxytocin antibodies. These data suggest that pineal peptides can participate in forming of reflect oxytocin release pattern. This pattern is initiated by suckling and is limited by oxytocin content in blood.

Topics: Administration, Intranasal; Animals; Animals, Suckling; Body Weight; Cattle; Drinking; Female; Lactation; Milk Ejection; Oxytocin; Peptides; Pineal Gland; Prolactin; Rats; Rats, Wistar

Selective serotonin (5-HT, 5-hydroxytryptamine) reuptake inhibitors (SSRIs) such as fluoxetine produce a gradual desensitization of hypothalamic post-synaptic 5-HT(1A) receptor systems. It is assumed that the effects of SSRIs on post-synaptic 5-HT(1A) receptors are mediated by 5-HT reuptake inhibition, leading to an increase of 5-HT in the synapse. However, there is no direct evidence to support this hypothesis.. The present study determined whether 5-HT(1A) receptor desensitization was mediated by fluoxetine's effects on serotonergic nerve terminals.. Serotonergic nerve terminals were destroyed by intracerebroventricular (i.c.v.) injection of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) combined with injection of the norepinephrine/dopamine reuptake inhibitor nomifensine. 5,7-DHT-induced loss of serotonergic terminals was confirmed by a 95% reduction in the density of [(3)H]paroxetine-labeled 5-HT transporters in the hypothalamus and a 97% reduction in the levels of 5-HT and 5-hydroxyindoleacetic acid in the cortex. Two weeks after the 5,7-DHT injections, rats were injected daily with fluoxetine (5 mg/kg or 10 mg/kg, i.p.) or saline for 14 days.. Injections of 10 mg/kg fluoxetine produced a significant decrease in body weight gain. Destruction of serotonergic nerve terminals reduced body weight and potentiated the ability of fluoxetine to further inhibit body weight gain. Increases in plasma levels of adrenal corticotrophic hormone (ACTH, corticotropin), corticosterone, and oxytocin after injection of the 5-HT(1A) agonist 8-hydroxy-2-dipropylaminotetralin [(+/-)8-OH-DPAT] were used as peripheral markers of 5-HT(1A) receptor function in the hypothalamus. In vehicle-pretreated rats, fluoxetine produced a dose-dependent reduction in the (+/-)8-OH-DPAT-induced increase in plasma ACTH and oxytocin levels. Destruction of serotonergic nerve terminals blocked the ability of fluoxetine to produce a desensitization in the ACTH, corticosterone, and oxytocin responses to (+/-)8-OH-DPAT.. The ability of fluoxetine to induce a desensitization of hypothalamic post-synaptic 5-HT(1A) receptor systems is dependent on the integrity of serotonergic nerve terminals in the hypothalamus, while its effect on body weight is not mediated by serotonergic nerve terminals in the hypothalamus.

Topics: 5,7-Dihydroxytryptamine; 8-Hydroxy-2-(di-n-propylamino)tetralin; Adrenocorticotropic Hormone; Animals; Body Weight; Cerebral Cortex; Corticosterone; Dose-Response Relationship, Drug; Fluoxetine; Hypothalamus; Injections, Intraventricular; Male; Oxytocin; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Selective Serotonin Reuptake Inhibitors; Serotonin

Oxytocin treatment may permanently alter endocrine axes resulting in anti-stress and anabolic effects. However, the nutritional status influences the effects of oxytocin. The specific aims of this study were to investigate the effects of postnatal oxytocin treatment on reproductive performance in adult life, by studying maternal weight gain, adiposity, plasma levels of IGF-I as well as fetal and placental weights in the following groups of animals: (1) Ad libitum fed dams coming from ad libitum fed mothers. (2) Ad libitum fed dams coming from food-restricted mothers. (3) Food-restricted dams coming from ad libitum fed mothers. (4) Food-restricted dams coming from food-restricted mothers. Oxytocin treatment postnatally had long-term effects and increased adiposity in pregnant dams and stimulated placental and fetal growth relative to saline-treated dams. However, if the dams themselves had been exposed to food restriction during fetal life, the effect of postnatal oxytocin treatment changed. The oxytocin-treated mothers were still fatter but had smaller fetuses. In conclusion, postnatal oxytocin treatment influences reproductive performance in later life but is dependent on the mother's previous and current nutritional experience.

Topics: Adipose Tissue; Animals; Body Weight; Female; Fetal Weight; Food Deprivation; Insulin-Like Growth Factor I; Litter Size; Male; Oxytocin; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction; Statistics, Nonparametric

We evaluated stillbirth risk factors in two commercial swine farms of the Rio Grande do Sul State (south of Brazil). The study was conducted during 1 month in Farm A and during 2 months in Farm B, both during 1999. Data for all farrowings that occurred during the study period were recorded (101 for Farm A and 373 for Farm B), without interference in the farm management. In Farm A, 39% of all litters born during the period of interest had stillborn piglets and the stillborn risk for piglets was 12%. In Farm B, 25% of all litters had stillborn piglets whereas the stillborn risk was 2%. Variables considered as potential risk factors for stillbirths were: parity (1, 2-3, 4+); breed (purebred or crossbred); sow body-condition (normal or fat); use of oxytocin during parturition (yes or no); obstetric intervention through vaginal palpation (yes or no); farrowing duration (<4 or > or =4h); mummified fetuses (yes or no); total litter size (<12 or > or =12 piglets); and litter birth weight (<11 or > or =11kg). All stillborn piglets had their classification validated by necropsy. In multivariable logistic-regressions, the cases were the litters having at least one stillborn piglet. In Farm A, litters having at least 12 pigs and in which oxytocin was used during the parturition had 20.8-times-higher odds of stillborn occurrence. In Farm B, litters from sows having parity > or =4 had 2.2-times-higher odds of stillborn occurrence than litters from parity 2 to 3 females, litters having > or =12 pigs had 2.0-times-higher odds of a stillborn piglet than smaller litters and farrowings in which vaginal palpation was performed had 8.0-times-higher odds. Farrowing room management to minimize stillborn risk should target higher-parity females, large litters and optimization of practices of obstetric interventions.

Topics: Animal Husbandry; Animals; Animals, Newborn; Birth Weight; Body Constitution; Body Weight; Brazil; Female; Fetal Death; Litter Size; Logistic Models; Oxytocin; Parity; Pregnancy; Pregnancy Complications; Risk Factors; Swine; Swine Diseases

To examine a possible sexual dimorphism in the osmotic control of arginine vasotocin (AVT) release in birds, age-matched male and female Japanese quail were subjected to water deprivation. The observed increased plasma osmolalities were accompanied by increased plasma AVT levels. Plasma mesotocin levels did not change with water deprivation. The sensitivity of the osmotic control of AVT release as determined by the slope of the relationship between plasma AVT levels and plasma osmolalities was significantly (P < 0.05) higher in males than in females. By Northern blot analysis, levels of hypothalamic AVT gene transcripts were increased 2.3 +/- 0.14- and 3.5 +/- 0.13-fold in water-deprived male and female Japanese quail, respectively, compared to normally hydrated birds. Our data suggest gender-related differences in the osmotic control of AVT release and in hypothalamic AVT gene expression in the Japanese quail.

Topics: Animals; Body Weight; Coturnix; Female; Gene Expression; Hypothalamus; Male; Osmolar Concentration; Oxytocin; Radioimmunoassay; RNA, Messenger; Sex Characteristics; Vasotocin; Water Deprivation

The aim of the present study was to investigate the anxiolytic effects of long-term treatment with fluoxetine in rats. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are used to treat anxiety and panic disorders, in addition to treating depression. A major concern with SSRIs is a 2-3-week delay in their therapeutic effects. SSRIs share with anxiolytic 5-HT(1A) agonists the ability to produce desensitization of post-synaptic 5-HT(1A) receptors. To investigate the anxiolytic effects of fluoxetine, rats were treated for 14 days with fluoxetine (10 mg kg(-1) day(-1), i.p. ). The rats were stressed using a conditioned stress procedure and tested one day after the last fluoxetine injection. Fluoxetine decreased stress-induced defecation (by 60%), reversed the stress-induced suppression of exploring behavior (by 59%) and shortened the duration of stress-induced freezing behavior (by 11. 5%). However, the stress-induced increase in plasma levels of ACTH, corticosterone, oxytocin, prolactin and renin were not inhibited by fluoxetine treatment. These findings suggest that neuroadaptive changes induced by sustained inhibition of serotonin (5-HT) reuptake, contribute to the mechanism of the anxiolytic effects of fluoxetine. In contrast, the neuroendocrine responses to conditioned stress are not affected by these neuroadaptive changes.

Topics: Adrenocorticotropic Hormone; Animals; Anxiety; Behavior, Animal; Body Weight; Conditioning, Psychological; Corticosterone; Defecation; Fluoxetine; Male; Neurosecretory Systems; Oxytocin; Prolactin; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Renin; Selective Serotonin Reuptake Inhibitors; Stress, Physiological

We sought to examine the relationship between epidural analgesia and cesarean and instrumental vaginal delivery rates.. This is a retrospective analysis of the first 1000 nulliparous pregnancies in women with a cephalic presentation in spontaneous labor at term in each of 3 different years, over which the epidural rate increased from 10% to 57%.. Cesarean and instrumental vaginal delivery rates were similar in all 3 years. Demographic characteristics remained unchanged or altered in a manner that has previously been associated with an increase in intervention. Electronic fetal monitoring and first-stage oxytocin use remained unchanged, but oxytocin use in the second stage increased considerably.. Increased use of epidural analgesia had no effect on cesarean delivery rates. Although randomized trials have suggested that it increases instrumental vaginal delivery rates, this might be overcome by active management of labor or judicious use of oxytocin in the second stage.

Topics: Adult; Analgesia, Epidural; Apgar Score; Birth Weight; Body Height; Body Weight; Cesarean Section; Cohort Studies; Female; Humans; Incidence; Infant, Newborn; Labor, Obstetric; Oxytocin; Pregnancy; Pregnancy Outcome; Retrospective Studies

The two genes coding for thyroid hormone receptors (TR) alpha 1 and beta have opposite effects on female sex behaviors. Deletion of TRalpha 1 reduced them, whereas deletion of TRbeta actually increased them. These results could not be attributed to altered levels of hormones in the blood, general alterations in estrogen responsiveness or altered general activity. Instead, they indicate a previously unknown molecular mechanism upon which the two TR genes exert opposite influences.

Topics: Animals; Body Weight; Estradiol; Estrogens; Female; Gene Deletion; Male; Mice; Mice, Inbred Strains; Mice, Knockout; Organ Size; Oxytocin; Paraventricular Hypothalamic Nucleus; Posture; Preoptic Area; Progesterone; Receptors, Estrogen; Receptors, Thyroid Hormone; Sexual Behavior, Animal; Thyroxine; Triiodothyronine; Uterus; Vasopressins

It was shown previously that luteinizing hormone-releasing hormone (LHRH) affects the neurohypophysial oxytocin release in water-deprived rats. However, the detailed mechanisms by which LHRH modifies the oxytocin response to hyperosmotic stimulation have not been explained so far. Using the isolated hypothalamo-neurohypophysial explants obtained from euhydrated rats, the effect of LHRH on the oxytocin secretion was studied under conditions of direct osmotic (i.e., Na(+)- evoked) as well as nonosmotic (i.e., K(+)-evoked) stimulation. Additionally, the oxytocin response to LHRH was investigated using the explants obtained from animals drinking 2% saline for eight days (systemic, i. e., both direct and indirect, osmotic stimulation). LHRH significantly enhanced Na(+)- and K(+)-evoked oxytocin release from explants taken from rats drinking tap water, indicating that LHRH could affect the Na(+)/K(+)-dependent depolarization of perikarya of oxytocin neurones. In contrast, LHRH significantly diminished the K(+)-stimulated hormone release when the neurohypophysial complex was obtained from previously salt-loaded rats, suggesting that peripheral osmotic stimulation somehow modifies the sensitivity of oxytocinergic neurones to LHRH (possible mechanisms are discussed). It is concluded that LHRH may participate in the regulation of oxytocin secretion via both direct and indirect impact on magnocellular oxytocinergic neurones depending on the current functional status of the hypothalamo-neurohypophysial complex.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Gonadotropin-Releasing Hormone; Hematocrit; Hypothalamo-Hypophyseal System; Hypothalamus; In Vitro Techniques; Male; Osmolar Concentration; Oxytocin; Pituitary Gland; Potassium; Rats; Rats, Wistar; Sodium Chloride; Sodium, Dietary

The aims of this study were: (1) to assess the effects of maternal undernutrition during pregnancy on adult offspring with regard to growth, body composition and plasma levels of glucose, insulin and corticosterone, and (2) to investigate whether oxytocin treatment early in life could ameliorate the adverse effects of food restriction in utero. Pups from ad libitum-fed and food-restricted (60% of ad libitum intake during pregnancy) rats were injected subcutaneously once a day with oxytocin or saline on days 1-14 after birth. At adult age (62 days), male offspring from food-restricted dams had lower body weight, less adipose tissue, lower plasma glucose but higher corticosterone levels, compared to offspring from ad libitum-fed dams. However, oxytocin-treated food-restricted males had higher body weight, higher glucose and lower corticosterone levels compared to their saline-treated counterparts. In conclusion, oxytocin treatment early in life seems to ameliorate some of the adverse effects of food restriction in utero.

Topics: Aging; Animals; Blood Glucose; Body Composition; Body Weight; Corticosterone; Female; Food; Food Deprivation; Insulin; Male; Oxytocin; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Weight Gain

The exact nature of how nitric oxide (NO) acts in the regulation of milk ejection during lactation is not clearly understood at the moment. In this study, we have examined the effect of drugs which spontaneously release NO (sodium nitroprusside, SNP) or inhibit the NO synthase (NOS) enzyme (Nomega-nitro-L-arginine, L-NA) on the activity of some hypothalamic and functionally associated nuclei using Fos expression as an index of neuronal activation. Lactating rats received intracerebroventricular injection of SNP, l-NA or vehicle (saline) just before they were reunited with their pups after a 12-h period of separation and allowed to suckle for 2 h. The difference in the total pup body weight before and after the period of suckling was used as a functional end-point of milk transfer. Central injection of SNP in conscious rats significantly inhibited Fos expression in the paraventricular nucleus (PVN), supraoptic nucleus (SON), periventricular and preoptic nuclei and also decreased pup body weight compared with saline- or l-NA-injected rats. Urethane-anesthetized animals, compared with their conscious counterparts, showed increased Fos expression in the PVN and SON. However, Fos expression in the PVN of the anesthetized animals was attenuated by l-NA injection compared with SNP and saline injection. Taken together with an earlier finding that SNP disrupts the milk ejection burst of oxytocinergic neurons, these observations suggest that NO may act within the neuron(s) possibly to alter the mechanism(s) regulating the periodic neuronal burst activity during lactation.

Topics: Anesthetics, Intravenous; Animals; Body Weight; Female; Hydrostatic Pressure; Injections, Intraventricular; Mammary Glands, Animal; Milk Ejection; Neurons; Nitric Oxide Donors; Nitric Oxide Synthase; Nitroarginine; Nitroprusside; Oxytocin; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Sulfhydryl Reagents; Supraoptic Nucleus; Urethane

The water-seeking behavior (WR) of toads (Bufo viridis) was investigated. Fully hydrated toads that are allowed free choice of wet or dry filter paper voluntarily and spontaneously select to sit on water-soaked paper at a regular frequency during trials. Dehydration of bladder-emptied toads by 14% elicits WR in all animals. Injection of aldosterone or angiotensin-I reduced the dehydration threshold to 7% weight loss. WR frequency increased when plasma osmolality was elevated by injection of NaCl or other solutes (both ionic and non-ionic). Only urea, to which cell membranes are highly permeable, was the exception that did not produce this response. The increase in WR frequency induced by elevated plasma osmolality was augmented by injection of aldosterone or angiotensin-I. In vivo water uptake, measured in a water bath, was increased by an NaCl or oxytocin injection, but not by aldosterone. It is concluded that elevated plasma osmolality induces an increase in WR frequency that is separate and prior to the water uptake process. Different hormones are involved in each step.

Topics: Aldosterone; Angiotensin I; Animals; Behavior, Animal; Body Weight; Bufonidae; Dehydration; Female; Male; Osmolar Concentration; Osmosis; Oxytocin; Skin Absorption; Sodium Chloride; Urea; Urinary Bladder; Water

Selective serotonin reuptake inhibitors, used widely in the treatment of depression, progressively inhibit sexual orgasm in many patients and induce a transient inhibition of sexual desire.. We attempted to model the effects of these drugs in sexually experienced male rats during tests of copulation in bilevel chambers. These chambers allow the study of both appetitive and consummatory sexual responses of male rats.. Males were treated daily with fluoxetine hydrochloride (0, 1, 5, or 10 mg/kg) and tested for sexual behavior with receptive females at 4-day intervals. Rats were treated with oxytocin (200 ng/kg) or saline after ejaculations had decreased.. Fluoxetine decreased ejaculatory responses of male rats in a dose- and time-dependent fashion, but left the copulatory efficiency of the males intact. In contrast, conditioned level changing, a measure of appetitive sexual excitement, was inhibited following acute and chronic treatment with 10 mg/kg, although tolerance may have developed to the effect of 5 mg/kg. Subsequent administration of oxytocin restored the ejaculatory response but not the measure of sexual excitement to baseline levels.. The reversal by oxytocin of the fluoxetine-induced deficit in ejaculations is consistent with the hypothesis that serotonin suppresses ejaculatory mechanisms by interrupting the action of oxytocin, which normally accompanies sexual behavior. Co-administration of oxytocin may help to alleviate the predominant sexual side effect of serotonin reuptake blockers.

Topics: Animals; Body Weight; Ejaculation; Fluoxetine; Male; Oxytocin; Rats; Rats, Long-Evans; Selective Serotonin Reuptake Inhibitors; Sexual Behavior, Animal

Annetocin is an earthworm oxytocin-related peptide that we previously isolated from the whole body of a lumbricid earthworm Eisenia foetida. We have reported that annetocin induces egg-laying-like behaviors in E. foetida and a gnathobdellid leech, Whitmania pigra, when it is injected into the respective animals. The present study was undertaken to probe physiological functions of invertebrate oxytocin-vasopressin-superfamily peptides with special reference to reproductive and osmoregulatory events in which vertebrate peptides of this superfamily are involved. Annetocin, Lys-conopressin (a leech vasopressin-related peptide) and two analog peptides, [Tyr(3)]-annetocin ((3)Y-annetocin) and [Phe(3)]-annetocin ((3)F-annetocin), were compared for their activities to induce egg-laying-like behavior and to change body weight as a measure of water balance in the leech W. pigra. Injection of annetocin, Lys-conopressin, and (3)F-annetocin caused both egg-laying-like behavior and reduction of body weight in the animals, but (3)Y-annetocin induced neither. Furthermore, leeches in the non-breeding season responded to peptides less conspicuously than those in the breeding season. Such a concomitant induction of egg-laying-like behavior and body-weight reduction suggests that these two phenomena are unitary and might be accounted for by the fact that egg-laying in leeches and earthworms is accompanied by secretion of a large quantity of mucus, which should significantly contribute to body-weight loss. J. Exp. Zool. 284:401-406, 1999.

Topics: Amino Acid Sequence; Animals; Body Weight; Female; Invertebrate Hormones; Leeches; Molecular Sequence Data; Oxytocin; Peptide Fragments; Peptides, Cyclic; Reproduction; Seasons; Water-Electrolyte Balance

The aims of this study were to investigate if administration of oxytocin to ad libitum fed and food-restricted female rats affects weight gain, body fatness, the IGF-axis, and some vagally mediated gastrointestinal hormones, such as gastrin, cholecystokinin (CCK) and somatostatin. Ad libitum fed and food-restricted (receiving 70% of the food intake of the ad libitum fed group) female rats were injected subcutaneously, once a day, for 10 days, with saline (control) or oxytocin (1 mg kg-1 bodyweight). The animals were killed 5 days after the last injection. Oxytocin-treated food-restricted females had more body fat and lower plasma levels of IGF-I, IGFBP-1 and IGFBP-3 compared with saline-treated counterparts. Oxytocin-treated ad libitum fed rats also had lower plasma levels of IGFBP-1 but contained less body fat, compared with saline-treated counterparts. There was no effect of oxytocin treatment on body weight or weight gain in either of the feeding groups. Except for gastrin, which was lower, there was no effect of oxytocin on the gastrointestinal hormones studied. The results indicate that oxytocin treatment influences fat deposition and the IGF-axis in female rats, but that the results are dependent on the nutritional status of the animal.

Topics: Animals; Body Weight; Eating; Female; Gastrointestinal Hormones; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Oxytocin; Rats; Rats, Sprague-Dawley

The effects of oxytocin on fetal and placental growth and on maternal weight gain and accumulation of body fat were studied in ad libitum-fed and food-restricted (receiving 70% of the food intake of the ad libitum-fed group) pregnant rats. Further, a possible role of the IGF axis in mediating oxytocin-induced changes was assessed. Pregnant rats were injected subcutaneously once a day during gestational d 1-5 with saline or oxytocin (1 mg/kg). Ad libitum-fed oxytocin-treated pregnant rats had higher circulating levels of IGF-I, larger placentas, fetuses, and newborn pups and contained less body fat at the end of pregnancy. In food-restricted dams, oxytocin-treatment had no effect on fetal and placental growth. Additionally, food restriction attenuated the normal increase in IGF binding protein-3 protease proteolysis during pregnancy. The results show that oxytocin may affect maternal adaptations to pregnancy and stimulate fetal growth. We suggest that this effect may be mediated by increased IGF-I in ad libitum-fed animals, whereas food restriction may block this effect by resulting in low levels of circulating IGF-I and by attenuating the pregnancy-associated increase in IGF binding protein-3 protease activity and, thereby, further compromise IGF bioavailability.

Topics: Adipose Tissue; Animals; Body Weight; Eating; Embryonic and Fetal Development; Female; Food Deprivation; Insulin-Like Growth Factor I; Oxytocin; Pregnancy; Rats; Rats, Sprague-Dawley

Responses of pituitary concentrations of vasopressin (AVP) and oxytocin (OT) during spaceflight have been variable, possibly due to differences in flight conditions or in age and strain of flight animals.. We reviewed findings of three space-flights of varying flight and recovery durations in which rats of different ages and strains were used. Male rats ranging in weight from 248-396 g were flown in space for 7-14 d. Flight animals were then compared with vivarium controls and synchronous controls. Parallel ground-based studies (hypergravity and simulated hypogravity) were conducted.. Pituitary content of AVP was significantly (p < or = 0.05) decreased by spaceflight (6.3 +/- 0.3 micrograms.mg-1 protein in flight vs. 8.3 +/- 0.5 micrograms.mg-1 protein in vivarium). OT content was also reduced during spaceflight (4.3 +/- 0.2 micrograms.mg-1 protein in flight vs. 6.1 +/- 0.3 micrograms.mg-1 protein in vivarium). Vivarium and synchronous control rats showed no difference in pituitary contents. Flight duration or recovery times did not appear to influence pituitary hormone contents. Strain of rat had an effect on content but not on responses to spaceflight. Age of animals confounded the response to spaceflight: pituitary contents of AVP and OT were not altered in young animals (< or = 60 d old). Hindlimb suspended animals showed no difference in AVP but OT content was decreased. Ground-based exposure to hypergravity (2 G) did not alter content of AVP or OT in young animals.. Decreases in pituitary content of AVP and OT with spaceflight may be due to a variety of factors unique to the microgravity environment. Differences between studies may be due in part to differences in size and age of rats used.

Topics: Age Factors; Animals; Body Mass Index; Body Weight; Confounding Factors, Epidemiologic; Hindlimb Suspension; Hypergravity; Hypogravity; Male; Oxytocin; Pituitary Gland; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Space Flight; Time Factors; Vasopressins

Previous studies have shown that preweanling rats do not express an endogenous sodium appetite until postnatal day 12. The present studies tested the hypothesis that prior to 12 days of age sodium appetite, induced by either central administration of angiotensin II (AngII) or adrenalectomy, is inhibited by endogenous oxytocin (OT). After 9- or 10-day old animals were given a central injection of either an OT receptor antagonist or vehicle, they were infused intraorally with 4% sodium chloride which the animals could either swallow or reject. Intake was measured as the increase from initial body weight. There was very little sodium consumption by vehicle-injected animals that received sham surgery or adrenalectomy; however, the OT receptor antagonist significantly elevated sodium consumption in adrenalectomized animals. The OT antagonist also potentiated sodium intake after AngII pretreatment. These results suggest that the neurochemical circuits necessary for the expression of sodium appetite are present and functional as early as postnatal day 9; however, until 12 days of age this behavior is suppressed by endogenous OT.

Topics: Adrenalectomy; Angiotensin II; Animals; Animals, Newborn; Appetite; Body Weight; Brain; Feeding Behavior; Milk; Oxytocin; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Sodium; Vasotocin

Rabbits nurse briefly only once each night and are frequently both pregnant and lactating. To investigate the influence of the daily timing of nursing on parturition, does (n = 10 per group) were remated after giving birth and were allowed to nurse under one of three schedules: group 1 every 24 h in the light, group 2 every 24 h in the dark, and group 3 at any time. Whereas does from groups 2 and 3 nursed and gave birth normally, does of group 1, forced to nurse out of phase with the normal schedule, showed disturbed nursing behavior and prolonged gestation followed by many stillbirths. In a second experiment, pregnant does (n = 10 per group) were treated daily either with oxytocin (OT) in the light (group 4), with OT in the dark (group 5), or with progesterone (P; group 6) or saline (group 7) in the light. All does gave birth normally except those of group 4, which responded similarly to group 1 does. These findings demonstrate that in the rabbit, parturition may be seriously compromised if does nurse out of phase with the normal schedule and suggest that a shift in the daily timing of OT release may underlie this.

Topics: Animals; Animals, Newborn; Birth Weight; Body Weight; Chinchilla; Female; Labor, Obstetric; Lactation; Maternal Behavior; Oxytocin; Pregnancy; Pregnancy, Animal; Progesterone; Rabbits; Time Factors

When low doses of insulin are infused directly into the third ventricle, rats reduce their food intake and lose weight. To determine whether these effects could be due to malaise induced by the treatment, the effects of intraventricular insulin were compared to the effects of the emetic agent lithium chloride to condition a taste aversion, to stimulate oxytocin secretion, and to reduce sodium appetite in response to furosemide treatment. For all three of these measures, lithium chloride treatment had a predictable effect compared to controls. Specifically, lithium caused a significant taste aversion, elevated plasma oxytocin, and attenuated sodium appetite. However, lithium did not produce a significant change in food intake or body weight. On the other hand, intraventricular insulin treatment did cause a significant reduction in body weight yet had no effect on these indices of malaise in the rat. These data are consistent with the hypothesis that intraventricular insulin does not reduce food intake and body weight by producing malaise but rather serves as a negative feedback signal of body adiposity to the central nervous system.

Topics: Animals; Appetite; Avoidance Learning; Body Weight; Dose-Response Relationship, Drug; Eating; Injections, Intraperitoneal; Injections, Intraventricular; Insulin; Lithium Chloride; Male; Oxytocin; Rats; Taste; Viscera; Water-Electrolyte Balance

1. Mature WL cockerels with permanent cannulae in brachial artery and vein were restrained in an isolated sling. Blood pressure (BP) and heart rate (HR) were continuously recorded. When the chickens were habituated to the sling, injections began. In each experiment the cockerels were injected intravenously 6 times at 6 min intervals. 2. In the first experiment 6 injections of 0.5 nmol[Aspl, Val5]ANG-II/kg body weight were given. 3. In the second experiment oxytocin (OT) antagonist ([d(CH2)5-O-Me-Tyr2,Thr4,Tyr9,Orn8]VT) at a dose of 2 nmol/kg, was injected for the first 3 and 0.5 nmol ANG-II/kg for the last 3 injections. Such OT-antagonist pretreatment completely abolishes the vasodepressor (VDP) response to neurohypophysial peptides in chickens. 4. Injections of ANG-II resulted in a biphasic effect on BP, an initial brief fall followed by a prolonged rise. During the hypotensive phase, tachycardia developed which turned into bradycardia as the hypertensive phase appeared. No tachyphylaxis of the VDP effect of ANG-II was evident with repeated injections. 5. OT-antagonist pretreatment had no effect on the VDP response to ANG-II. 6. These results suggest that, unlike relaxation of chicken aortic ring in in vitro preparations, there is no tachyphylaxis of the VDP response to ANG-II, in vivo. Furthermore, the neurohypophysial peptides are not involved in the VDP effect of ANG-II because pretreatment with an OT-antagonist had no effect on it. The baroreflex buffers the effects of ANG-II on vascular tone by affecting HR. 7. As ANG-II is secreted during hypovolaemia, the biphasic haemodynamic response peptides may have a compensatory role following volume contraction.

Topics: Angiotensin II; Animals; Blood Pressure; Body Weight; Bradycardia; Cardiovascular Physiological Phenomena; Cardiovascular System; Chickens; Heart Rate; Hemodynamics; Male; Oxytocin; Tachycardia; Vasoconstrictor Agents

The lasting effects of a 9-day neonatal exposure to vasopressin and oxytocin were examined in the rat to discover if peptide administration results in organizational effects. When tested in young adulthood, brain growth, not body growth, appeared to be impaired. Basal and challenge tests of urine production, carried out to see the development of the hormonal antidiuretic function of vasopressin, revealed no lasting changes, and therefore did not confirm earlier findings of an induced mild polyurea. Behavioral testing of learning by making use of a one-trail step-through paradigm with a 24-h retention trial--a test that is sensitive to vasopressin--did not show impairments. Open field tests, however, showed enhanced emotionality in the vasopressin-treated females, as well as an initially increased ambulation in the males, and increased grooming in both sexes, the latter also having been reported to be induced by vasopressin administration in the septal areas. Oxytocin treatment did not produce lasting changes. Our conclusion, therefore, is that peripherally circulating vasopressin can affect the organizational development of the rat brain. It remains to be established whether this is an effect obtained through changes in the general peripheral physiology or a reflection of plasticity phenomena at the level of central vasopressin neurotransmission.

Topics: Animals; Animals, Newborn; Behavior, Animal; Body Weight; Brain; Eye; Female; Learning; Male; Oxytocin; Rats; Rats, Wistar; Retention, Psychology; Sex Characteristics; Urine; Vasopressins

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent known anorexigens with an unestablished mechanism of action. In the present study, the role of nausea in TCDD-induced hypophagia was assessed by a battery of behavioral (conditioned taste aversion [CTA], kaolin consumption, protein selection), biochemical (plasma oxytocin), and antiemetic drug intervention (trimethobenzamine, metoclopramide) approaches. Moreover, both the most TCDD-susceptible (Long-Evans [L-E]; IP LD50 approximately 10 micrograms/kg) and the most TCDD-resistant (Han/Wistar [H/W]; IP LD50 > 3000 micrograms/kg) rat strains were employed in the experiments. L-E rats were exposed to a lethal dose of TCDD (50 micrograms/kg), whereas H/W rats were treated with high but nonlethal doses (50 or 1000 micrograms/kg). TCDD produced a positive CTA response in H/W rats alone. These animals also increased their kaolin consumption more than L-E rats of either gender after TCDD exposure. TCDD decreased the proportional intake of energy from high-protein diet in female L-E rats, but tended to increase it in male L-E and H/W rats. TCDD did not affect plasma oxytocin concentration by itself, but potentiated the elevation caused by the positive control compound, LiCl, in L-E rats on day 8. Neither antiemetic tested had any detectable influence on TCDD-induced wasting. These findings imply that the degree of nausea elicited by TCDD in the rat depends on strain and gender. However, nausea has only a minor, if at all, causal role in the lethal wasting syndrome characteristic of this compound.

Topics: Animals; Antiemetics; Benzamides; Body Weight; Eating; Energy Metabolism; Female; Kaolin; Male; Metoclopramide; Nausea; Oxytocin; Polychlorinated Dibenzodioxins; Rats; Rats, Inbred Strains; Rats, Wistar; Taste

Angus x Hereford multiparous cows were assigned to four treatments: 1) mastectomized+calf weaned at birth (MCW; n = 7); 2) mastectomized+calf presence restricted to noninguinal contact (MCR; n = 7); 3) mastectomized+unrestricted calf presence (MCP; n = 7); and 4) udder-intact cows+unrestricted calf presence (UICP; n = 8). Except for MCW cows, cow-calf pairs were penned together individually from parturition (d 0) until d 35 when calves were weaned. On d 7, calves in MCP and UICP treatments were separated overnight from their dams, and before and upon reunion, blood samples were collected from the cows to assess changes in oxytocin, cortisol, and prolactin. Calves in the MCP and UICP treatments attempted to or suckled their dams for a similar duration upon reunion, respectively. Concentrations of cortisol and percentage of change in oxytoxin and prolactin were increased (P < .05) for up to 12 min in MCP cows after reunion with their calves. Average concentrations of serum LH in samples collected on d 14, 21, 28, and 35 did not differ in noncyclic cows among treatments within day postpartum (except for greater [P < .05] LH in MCW cows on d 21). However, MCP cows had more (P < .05) LH pulses (d 21), greater (P < .05) variability in LH pulses (d 21), greater (P < .05) variability in LH concentrations, and greater (P < .05) average maximum concentrations of LH than UICP cows after d 14. Intervals to first ovulation were similar in MCW and MCR cows but shorter (P < .01) than those in MCP and UICP cows. Attempted suckling of mastectomized dams by their calves was associated with increased serum cortisol and percentage of increase in serum oxytocin and prolactin. Despite increased LH in MCP cows, intervals to first ovulation did not differ from those of UICP cows.

Topics: Animals; Body Weight; Cattle; Estrus; Female; Hydrocortisone; Lactation; Luteinizing Hormone; Mammary Glands, Animal; Mastectomy; Maternal Behavior; Ovulation; Oxytocin; Progesterone; Prolactin; Random Allocation

A large number of oxytocin (OT)-like neurons were detected in the sex segmental ganglia (SG5, SG6) of three species of leeches belonging to different orders: Theromyzon tessulatum, Hirudo medicinalis and Erpobdella octoculata. In this latter species, an epitope close to the vertebrate OT by its C-terminal part (MSH release inhibiting factor: MIF), localized in granules of a size diameter of ca 120 nm and colocalized with FMRFamide(FMRFa)-like material was demonstrated. With reverse phase-high performance liquid chromatography, evidence was given that the two epitopes (OT and FMRFa) colocalized in the same neurons were biochemically different. A titration of OT per SG indicated that the OT-like amount was considerably higher in sex SG than in non-sex SG (ca. 5 pmol vs. ca. 0.5 pmol). Moreover, at the level of sex SG, this amount was ca. 3-fold higher in immature leeches than in mature specimens. Injections of extracts of SG of E. octoculata and of fragments of OT (Tocinoic acid or MIF) to T. tessulatum, indicated that MIF (the epitope found in the sex SG) and sex SG have the same anti-diuretic effect on the leeches injected. These results pointed to an anti-diuretic role of the leech OT-like substance.

Topics: Animals; Body Weight; Chromatography, High Pressure Liquid; Diuresis; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Fluorescent Antibody Technique; FMRFamide; Ganglia; Immunohistochemistry; Leeches; Male; MSH Release-Inhibiting Hormone; Neurons; Neuropeptides; Neurotransmitter Agents; Oxidation-Reduction; Oxytocin; Radioimmunoassay; Tissue Extracts

Anorexia nervosa is associated with vasopressin, oxytocin and serotonin abnormalities. Because of the relationship between exercise and anorexia nervosa, we explored the weight-loss syndrome produced by wheel running in food-deprived rats. Its effects on regional vasopressin and oxytocin concentrations were determined under basal conditions and following systemic fluoxetine. Weight-matched, exercised and unexercised rats served as controls. Fluoxetine caused abnormalities in suprachiasmatic vasopressin and dynorphin A content and in thymus oxytocin content that did not occur in weight-matched or exercised controls. No syndrome-specific anomalies occurred in the hypothalamo-neurohypophysial system or dorsal vagal complex (DVC). However, weight reduction and fluoxetine increased circulating vasopressin; moderate exercise caused fluoxetine-induced elevations in posterior pituitary vasopressin and oxytocin; and, unlike the other groups, fluoxetine increased DVC oxytocin in freely fed unexercised rats. It was concluded that syndrome-specific vasopressin and oxytocin abnormalities occur that are not secondary to weight loss or moderate exercise; that weight loss or fluoxetine increases circulating vasopressin; that moderate exercise alters neurohypophysial vasopressin and oxytocin content; and that weight loss or exercise inhibits a fluoxetine-stimulated increase in DVC oxytocin. Finally, it was argued that the fluoxetine abnormalities indicate possible serotonin dysfunction in the syndrome.

Topics: Animals; Anorexia Nervosa; Behavior, Animal; Body Weight; Dynorphins; Eating; Fluoxetine; Male; Oxytocin; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Suprachiasmatic Nucleus; Supraoptic Nucleus; Vagus Nerve; Vasopressins

The neurons of the supraoptic nucleus in the rat hypothalamus are reported not to possess receptors for gonadal steroids and sexual dimorphism has not previously been described in this nucleus. We have analysed this nucleus in groups of Sprague-Dawley rats (six males or six females per group), one, two, six, 12 and 18 months after birth. Body and brain weights were recorded, the volume of the nucleus was determined from the right hemisphere and all other quantitative parameters were determined from the left nucleus. In addition, different groups of four male and four female rats aged two and 18 months were analysed after immunocytochemical staining to distinguish between vasopressin and oxytocin neurons. The total number of neurons was constant in all groups studied, despite which the volume of the supraoptic nucleus increased progressively with age in both males and females. The cross-sectional areas and volumes of supraoptic neurons also increased with age. The volume density of the neuropil remained constant in all groups and there was a progressive decrease with age in the numerical density of neurons. Immunocytochemistry revealed that the age-dependent increases in the size of the neurons involved primarily the vasopressin neurons. The age-related changes were much greater in males than in females, resulting in significant differences between the sexes at two, six, 12 and 18 months with respect to the volume of the supraoptic nucleus, the cross-sectional areas of neuronal somata and nuclei, and the volume of supraoptic neurons. Thus the supraoptic nucleus and its vasopressin neurons are larger in adult males than in age-matched females. Since we have also shown that body weight is very closely correlated with changes in the size of supraoptic neurons, and adult male rats are heavier than females of the same age, we suggest that these size changes reflect adaptation of the vasopressin neurons of the supraoptic nucleus to increasing functional demands associated with the regulation of water balance in bodies of increasing size.

Topics: Aging; Analysis of Variance; Animals; Body Weight; Female; Immunohistochemistry; Male; Neurons; Organ Size; Oxytocin; Rats; Rats, Sprague-Dawley; Sex Characteristics; Supraoptic Nucleus; Vasopressins

Prenatal stress in rats usually results in behavioral and developmental changes in offspring. This experiment assessed body weight during the first three weeks postpartum and subsequent behavior of the offspring when tested as adults. Pregnant females allocated to the stress condition were exposed during the third week of pregnancy to either predictable (NOV1) or unpredictable (NOV2) psychological novelty stress. At this time, pregnant rats were also treated with various doses of oxytocin or vehicle solution. The exposure to unpredictable novelty stress during the third week of pregnancy resulted in pups which were significantly heavier at birth than either control animals or those which had received predictable exposure to the novelty stress. In contrast, oxytocin treatment appeared to lower body weight of offspring compared to control animals. This effect was observed right up until Day 21 postpartum for animals exposed to the larger dose (11.6 I.U.) of oxytocin. When tested as adults, NOV1 and NOV2 offspring were found to defecate more in the open field setting suggesting the they were more emotional than control animals. It was concluded that psychological stress during pregnancy has a subtle effect on development and subsequent effects on later emotionality of the offspring when tested as adults.

Topics: Adrenocorticotropic Hormone; Animals; Animals, Newborn; Behavior, Animal; Birth Weight; Body Weight; Brain; Exploratory Behavior; Female; Oxytocin; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Sex Factors; Stress, Psychological

Recent evidence has implicated hypothalamic peptides, such as arginine vasopressin (AVP) and oxytocin (OT) in the control of feeding behavior. In this study, we investigated the impact of food deprivation (48 h) and subsequent refeeding (6 h) on the concentration of AVP and OT in discrete hypothalamic areas, as well as in the neurohypophysis. We also estimated in these rats certain peripheral measures, including hydroelectrolytic parameters, plasma and urine AVP, and plasma corticosterone. The results of this study revealed that food deprivation for 48 h produced little change in OT concentration in the various hypothalamic nuclei studied, including the paraventricular and supraoptic nuclei, with the exception of the median eminence (ME), where a significant decline (-36%; p < 0.05) was detected. This effect was not significantly reversed by 6 h of refeeding. With respect to AVP concentration, food deprivation caused a reliable decline exclusively in the parvocellular subdivision of the paraventricular nucleus (pPVN; -45%; p < 0.01) and in the supraoptic nucleus (SON; -45%; p < 0.01). No change in AVP was detected in the ME or in most other hypothalamic nuclei examined. Refeeding for 6 h actually potentiated the effect of food deprivation, decreasing further from baseline the content of AVP in the pPVN and SON. The only other hypothalamic area to exhibit a change in AVP content was the ventromedial nucleus, where AVP level increased (p < 0.001) after deprivation and declined to normal after 6 h of refeeding. The content of AVP and OT in the neurohypophysis was unaffected by food deprivation and subsequent refeeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Blood Glucose; Blood Urea Nitrogen; Body Weight; Brain Chemistry; Corticosterone; Creatinine; Eating; Food Deprivation; Hypothalamus; Male; Oxytocin; Pituitary Gland, Posterior; Potassium; Rats; Rats, Sprague-Dawley; Sodium

Heat-stressed pregnant ewes deliver intrauterine growth-retarded lambs. Selected maternal and fetal changes were investigated during acute heat stress in order to elucidate the mechanism for this growth retardation. Uterine blood flow decreased 20 to 30% in pregnant ewes during 1 degree C increases in core temperature. The decreases were accompanied by 60 and 100% increases in serum oxytocin and antidiuretic hormone, respectively. These effects were mimicked by salt loading or injections of antidiuretic hormone or oxytocin, suggesting a role for either or both hormones in regulating uterine blood flow during pregnancy. Chronically heat-stressed pregnant ewes were delivered by Caesarean section. Their fetuses were approximately 20% smaller than thermoneutral controls. Within each pair of heat-stressed twins, one fetus weighted one-third less than its litter mate. No difference in weights were observed within the control twins. The livers and brains of the heat-stressed fetuses were disproportionate in size. The livers from the small heat-stressed twins contained only one-half the protein of the controls and one-fourth the protein of their litter mates. Muscle protein was decreased in the heat-stressed fetuses, and liver and muscle glycogen were elevated as were liver arginase, glutamate-pyruvate transaminase and muscle creatinine. These results are consistent with the following hypothesis: heat stress stimulates the release of maternal antidiuretic hormone or oxytocin, which reduces uterine blood flow and causes a shift in fetal metabolism from anabolic to catabolic pathways; one fetus of heat-stressed twins is more severely affected than its litter mate.

Topics: Animals; Body Weight; Female; Fetal Growth Retardation; Hot Temperature; Litter Size; Myocardium; Organ Size; Oxytocin; Pregnancy; Pregnancy Complications; Regional Blood Flow; Sheep; Sheep Diseases; Stress, Physiological; Uterus; Vasopressins

Spontaneous manipulator and locomotor activities, food and fluid intake have been recorded from rats suffering from a genetic lack of central vasopressin (VP) synthesis (Brattleboro strain, DI), their heterozygous litter mates (HZ) or Long Evans (LE) rats. The daily patterns of activities did not differ, except for their drinking behavior. This was mainly associated with food intake during the dark period with LE rats but was distributed equally during light and dark periods with DI rats. HZ rats showed a behavioral heterogeneity, some of them following the daily pattern of LE rats, and others, that of DI rats. The daily feeding pattern was identical in the three genotypes but the selection between two isocaloric contrasted diets was different. When they were fed ad lib, HZ and DI rats consumed less carbohydrate than LE rats, the protein intake being unchanged. On the contrary, when the DI rats were only fed during the dark period, they ate more carbohydrate than LE rats. The peripheral infusion of a V2 AVP agonist (dDAVP) restored a normal hydric balance in DI rats but failed to modify the diet selection. These data show that in the rats, the lack of central VP synthesis disturbs both the selection of diets and the efficiency of the satiety signals. These disturbances were unchanged by the peripheral VP treatment which suggested the direct involvement of the central release of the neuropeptide.

Topics: Animals; Arginine Vasopressin; Body Weight; Circadian Rhythm; Deamino Arginine Vasopressin; Dietary Carbohydrates; Dietary Proteins; Drinking; Eating; Hypothalamo-Hypophyseal System; Male; Motor Activity; Oxytocin; Psychomotor Performance; Rats; Rats, Brattleboro; Water-Electrolyte Balance

In order to resolve conflicting reports in the literature on the effect of aging on the hypothalamo neurohypophyseal system (HNS) in rats, multiple parameters associated with the HNS were evaluated in young (4 months), fully mature (14 months), and old (25 months) Fischer 344 rats under basal and stimulated conditions. The hypothalamic hormones oxytocin and vasopressin were compared in radioimmunoassay of serum, urine, brain and pituitary. Information on body weight, water intake, urine output, serum hematocrit and plasma osmolality was also obtained from the same subjects and analyzed together with these data. Finally, semi quantitative histofluorescence assessment of the noradrenergic innervation of the mediobasal hypothalamus from the same animals was performed to determine the extent of central afferent input to the HNS with advancing age. The circulating levels of vasopressin and oxytocin did not significantly differ in the three age groups under basal conditions. Serum vasopressin concentration was increased following water deprivation, and the increase was comparable in all age groups. Serum oxytocin was also increased following water deprivation in all groups, but the increase was greater in the 25-month-old rats relative to the 4-month-old rats. Urinary excretion of vasopressin was used as an index of daily vasopressin secretion. The urinary concentration of vasopressin was less in aged rats relative to young controls, though an increased urine volume in the mature and old animals meant that total vasopressin excretion in the urine was comparable at all ages studied. The increased urine volume in the mature and aged rats does not appear to reflect a decrease in renal sensitivity to vasopressin, since all age groups demonstrated a comparable reduction in urine volume during water deprivation, at comparable concentrations of circulating vasopressin. These data suggest that the increase in urine volume observed in the 14- and 25-month-old rats may be a function of increased fluid intake rather than hyperactivity in the HNS. The concentrations of both peptides were reduced in the posterior pituitary of aged rats, though again, the total amount of peptide in the gland did not change. Only oxytocin showed an age-related change in the hypothalamus, decreasing in the oldest subjects. These data indicate that the ability to secrete adequate quantities of vasopressin in response to dehydration is not compromised in Fisher 344 rats up to 25 months of age.

Topics: Aging; Animals; Body Weight; Catecholamines; Drinking; Hematocrit; Male; Microscopy, Fluorescence; Osmolar Concentration; Oxytocin; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Posterior; Radioimmunoassay; Rats; Rats, Inbred F344; Supraoptic Nucleus; Vasopressins

Oxytocin is a hypothalamic neuropeptide with both centrally and peripherally directed pathways. Data from experimental animals indicate that oxytocin impairs consolidation of aversively conditioned behaviors and is released after feeding or experimental gastric distension. The authors report that the mean CSF oxytocin level of five underweight women with restricting anorexia, but not 12 underweight bulimic anorexic women or 35 normal-weight women with bulimia nervosa, was significantly lower than the level of 11 control subjects. Restricting anorexic patients' low CSF oxytocin levels may reflect their persistently low food intake, and this behavior may exacerbate their tendency for perseverative preoccupation with adverse consequences of food intake.

Topics: Adult; Anorexia Nervosa; Body Weight; Bulimia; Eating; Female; Humans; Oxytocin

The response of the adrenal zona fasciculata (ZF) and zona reticularis (ZR) to oxytocin (OT) was examined in male rats using a stereological method. The 10-day administration of 0.25 IU OT/100 g daily caused an enlargement of ZF due to cell hypertrophy associated with striking lipid accumulation. The volume of ZR was decreased, this change being the consequence of the reduced cell population. The possible site of OT action is discussed.

Topics: Adrenal Glands; Animals; Body Weight; Hydrocortisone; Male; Organ Size; Oxytocin; Rats; Rats, Inbred Strains; Zona Fasciculata; Zona Reticularis

The effects of streptozotocin-induced diabetes on weight gain, bone growth and GH secretion have been studied in conscious chronically cannulated male rats. In addition to the classic diabetic symptoms (hyperphagia, polydipsia, polyuria, glycosuria and hyperglycaemia), the slow body weight gain (0.95 +/- 0.5 compared with 2.63 +/- 0.5 g/day in non-diabetic controls) was associated with a reduction in bone growth (from 162 +/- 9 to 48 +/- 4 microns/day) and a reduced pituitary GH content (from 1.5 +/- 0.2 to 0.6 +/- 0.06 mg/gland). Serial blood sampling during the day or overnight showed that the normal male episodic GH secretory pattern was obliterated in the diabetic animals. The constant osmotic stimulation of hyperglycaemia and high fluid turnover was reflected in a significant reduction in pituitary oxytocin and arginine vasopressin (AVP) stores. Intravenous insulin infusions (67-1340 pmol/h for 4 or 7 days) caused a large initial weight gain (greater than 20 g in 2 days) followed by a slower increase, and stimulated tibial bone growth (to 100 +/- 16 and 126 +/- 8 microns/day after 4 or 7 days respectively). Insulin infusion for 7 days also increased pituitary GH content (to 1 +/- 0.15 mg/gland), and the normal episodic GH secretory pattern returned. Intravenous infusions of insulin which reduced, but did not completely normalize, blood glucose levels, allowed the resumption of growth and pulsatile GH secretion. Continuous infusion of recombinant human insulin-like growth factor-I (hIGF-I) at 1110 pmol/h for 54 h also caused a large initial rise in body weight in diabetic rats (17.1 +/- 1.6 compared with 7.5 +/- 2.8 g in saline-infused controls) due primarily to increased fluid retention. This effect of hIGF-I occurred without any significant changes in pituitary GH, AVP, oxytocin, blood glucose or bone growth over this short-term infusion, nor was there any obvious effect on spontaneous GH secretion, monitored over the entire infusion period. We conclude that the diabetic rat is not a good model to study growth stimulation by short-term insulin or IGF-I treatments because the insulin-like effects of these peptides obscure their specific growth-promoting activities in this model.

Topics: Animals; Arginine Vasopressin; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Eating; Growth Hormone; Insulin; Insulin-Like Growth Factor I; Male; Oxytocin; Pituitary Gland; Rats; Rats, Inbred Strains; Somatomedins; Time Factors

In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.

Topics: Animals; Body Weight; Diet; Gastrins; Male; Obesity; Organ Size; Oxytocin; Pancreatic Polypeptide; Prostheses and Implants; Rats; Rats, Inbred Strains; Stomach

1. Administration of 10 micrograms kg-1 of the long lasting potent kappa- and weaker mu-opioid agonist N-(cyclopropylmethyl)-19-isopentylnororvinol (M320) twice daily from day 20 of gestation prolonged the internal gestation period of the rat and retarded the development of the offspring in the perinatal period. 2. The capacities of myometrial, placental and cervical tissues to produce prostaglandin E2 (PGE2) were not affected by M320 treatment. 3. During the period in which parturition normally occurred in saline-treated rats, foetal pituitary levels of immunoreactive oxytocin (ir-OXY) but not immunoreactive arginine-vasopressin (ir-AVP) were greater in M320-compared to saline-treated animals. Following the completion of parturition, foetal pituitary ir-OXY and ir-AVP levels continued to rise in saline-treated rats, but fell dramatically in rats treated subacutely with M320. 4. These data indicate that subacute treatment with M320 may inhibit foetal oxytocin release at term. This foetal OXY release may be a stimulus for the initiation of labour.

Topics: Animals; Arginine Vasopressin; Body Weight; Cervix Uteri; Dinoprostone; Female; Gestational Age; Labor, Obstetric; Morphinans; Myometrium; Oxytocin; Pituitary Gland; Placenta; Pregnancy; Radioimmunoassay; Rats; Rats, Inbred Strains; Time Factors

The response of plasma oxytocin to an iv bolus injection of crystalline insulin (0.15 U/kg) was evaluated in 14 normal weight [mean body mass index (BMI) = 23] and in 9 obese (mean BMI = 42) men. Similar blood glucose decrements after insulin injection were observed in the two groups. Obese and normal weight subjects presented similar basal oxytocin levels. In both groups, oxytocin rose significantly during the insulin tolerance test (ITT); however, the peak oxytocin response in the obese men was significantly lower than in the normal weight subjects. Obese men were restudied after substantial weight loss. Basal oxytocin levels and glucose response to insulin did not change after weight reduction. The oxytocin response to the ITT was significantly higher than before slimming and did not differ from that observed in the normal weight subjects. A significant negative correlation between BMI values and oxytocin peak levels during ITT was observed in the lean controls and obese subjects (r = 0.516, p less than 0.02). These results demonstrate that in obese subjects the oxytocin secretory response during an insulin tolerance test is reduced, suggesting the existence of a hypothalamic-pituitary disorder in obesity.

Topics: Adult; Antibodies; Blood Glucose; Body Weight; Humans; Hypoglycemia; Injections, Intravenous; Insulin; Male; Obesity; Oxytocin; Radioimmunoassay; Time Factors

1. Acutely, opioids inhibit oxytocin secretion. To study the responses of oxytocin neurones during chronic opioid exposure, forty-five lactating rats were infused continuously from a subcutaneous osmotically driven mini-pump via a lateral cerebral ventricle with morphine sulphate solution from day 2 post-partum for 5-7 days; the infusion rate was increased 2- or 2.5-fold each 40 h from 10 micrograms/h initially up to 50 micrograms/h; controls were infused with vehicle (1 microliter/h, twenty-eight rats) or were untreated (eight rats). 2. Maternal behaviour was disrupted in 27% of the morphine-treated rats; in rats that remained maternal morphine did not affect body weight or water intake but increased rectal temperature by 0.82 +/- 0.14 degrees C (mean +/- S.E.M.) across the first 4 days. 3. Weight gain of the litters of maternal morphine-treated rats was reduced by 32% during 7 days, predominantly in the first day of treatment when milk transfer was also reduced. Observation of pup behaviour during suckling showed decreased frequency of milk ejections on only the second day of morphine treatment. Plasma concentration of prolactin after 6 days was similar in maternal morphine-treated and control rats, but reduced by 90% in non-maternal morphine-treated rats, indicating normal control of prolactin secretion by suckling in morphine-treated rats. 4. Oxytocin and vasopressin contents, measured by radioimmunoassay, in the supraoptic and paraventricular nuclei and in the neurohypophysis were similar between fourteen maternal morphine-treated, twelve vehicle-treated and eight untreated lactating rats; thus exposure to morphine did not involve increased production and storage of oxytocin. 5. Distribution of [3H]morphine infused intracerebroventricularly into six virgin female rats for 6 days was measured by scintillation counting of tissue extracts. Morphine concentration in the hypothalamus and neurohypophysis was 2.7 and 12.8 micrograms/g, respectively, and in blood plasma 0.75 micrograms/g. Tolerance was not due to failure of morphine infusion. In addition, naloxone (5 mg/kg s.c.) provoked typical withdrawal reactions ('wet dog' shakes, defaecation, burrowing) in lactating rats infused with morphine for 5 days. 6. Pups were suckled onto seven maternal morphine-infused and five vehicle-infused rats anaesthetized with urethane for recording of intramammary and arterial blood pressures after treatment for 5 days. The incidence and pattern of milk ejections, and m

Topics: Animals; Body Weight; Carbachol; Cerebral Ventricles; Drug Tolerance; Female; Infusions, Parenteral; Lactation; Maternal Behavior; Milk Ejection; Morphine; Morphine Dependence; Naloxone; Neurons; Oxytocin; Pregnancy; Rats

We have investigated the role of the area postrema (AP) in mediating the neurohypophyseal hormone response to peripheral administration of nausea-producing agents in rats. In control animals, lithium chloride (LiCl) and apomorphine (APO) caused a rise in plasma levels of immunoreactive oxytocin (OT) and arginine-vasopressin (AVP), whereas sulphated cholecystokinin octapeptide (CCK-8s) stimulated OT secretion only. Rats with AP lesions exhibited a similar OT and AVP response to LiCl and APO but the OT response to CCK-8s was significantly diminished. The results indicate that the selective stimulation of OT secretion by CCK-8s is partly mediated via the AP. Although the nausea-producing effects of LiCl and APO may involve the AP, the neuroendocrine effects of these agents may well be mediated via actions outside the AP.

Topics: Animals; Apomorphine; Arginine Vasopressin; Body Weight; Cerebral Ventricles; Chlorides; Lithium; Lithium Chloride; Male; Oxytocin; Rats; Rats, Inbred Strains; Sincalide

The Brattleboro rat has severe diabetes insipidus due to an autosomal recessive trait resulting in the inability to synthesize detectable amounts of hypothalamic vasopressin. To determine whether this abnormality is due to a regulatory defect in the Brattleboro rat's vasopressin gene, we studied changes in the hypothalamic content of vasopressin mRNA in normal Long-Evans and homozygous Brattleboro rats subjected to osmotic stress and correlated these changes with systemic responses to water deprivation. We report that the Brattleboro rat does have a marked defect in the regulation of vasopressin gene expression consisting of an inability to increase hypothalamic vasopressin mRNA content in response to severe osmotic stress.

Topics: Animals; Body Weight; Gene Expression Regulation; Hypothalamus; Osmolar Concentration; Oxytocin; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Mutant Strains; RNA, Messenger; Vasopressins; Water Deprivation

At 8 and 13 days post partum, rats have the same total milk availability; yet, in response to suckling they release a greater amount of milk on day 13 than on day 8. Increased sensitivity to suckling in the more advanced lactators may result from a greater release of oxytocin or from changes in the mammary glands as lactation advances. The present study explores this latter possibility in anaesthetized dams at 8-9 and 13-15 days of lactation. Milk release and intramammary pressure were measured in anaesthetized dams in response to various doses of oxytoxin. Milk release was determined from the body weight gain of pups which had been fasted for 5 h before suckling on dams which had been isolated for 5 h. This parameter was significantly greater in 13- to 15-day lactators than in 8- to 9-day lactators over the range of oxytocin doses examined. In contrast, intramammary peak pressure and its dissipation time were significantly larger in the 8- to 9-day lactators than in the 13- to 15-day lactators. The compliance of the mammary glands was indirectly assessed at the two stages of lactation. When a constant pressure pulse was introduced into a cannulated gland, the resulting pressure peak was significantly greater in 8-day than in 13-day lactators, indicating a greater resistance in the former. Taken together, these results indicate that when endogenous oxytocin is inhibited (by anaesthesia) the greater milk release observed at the later stage of lactation in response to various doses of oxytocin may be due to a decline in mammary resistance as lactation progresses.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Female; Lactation; Mammary Glands, Animal; Milk Ejection; Oxytocin; Pregnancy; Pressure; Rats; Rats, Inbred Strains; Time Factors

The effects of chronic infusion of porcine relaxin on oxytocin release were studied in lactating rats. Infusion of relaxin (4.2 micrograms/h for either 4 or 6 days) suppressed reflex milk ejection and reduced litter weight gain for 48 h compared with saline-infused controls. After 2 days, neither the rate of growth nor the frequency of milk ejection were significantly different from controls. For 24 h after the infusion of relaxin ended, litters gained weight more quickly than controls but there was no difference seen in the frequency of milk ejection. The effects on oxytocin release of stopping an infusion of relaxin after 3 days were investigated. There was a significant (P less than 0.01) rise in plasma oxytocin (up to 90 pmol/l) 30 min after the infusion was stopped, followed by a sustained rise in intramammary pressure. Treatment of relaxin-infused rats with naloxone (0.1 mg/kg) when the infusion was halted caused a more rapid release of oxytocin (within 2 min), a greater release of oxytocin (up to 140 pmol/l) and a prolonged rise in intramammary pressure.

Topics: Animals; Body Weight; Female; Lactation; Mammary Glands, Animal; Milk Ejection; Naloxone; Oxytocin; Pregnancy; Pressure; Rats; Relaxin

A slight but significant natriuretic action of 1-24 ACTH was confirmed both in trained conscious nonhydrated rats and in anaesthetized rats with sustained water diuresis. This action was compared with a strongly effective oxytocin analogue, nacartocin.

Topics: Adrenocorticotropic Hormone; Animals; Body Weight; Cosyntropin; Dose-Response Relationship, Drug; Male; Natriuresis; Oxytocin; Potassium; Rats; Rats, Inbred Strains; Sodium

In order to see whether the mother contributes to the vasopressin or oxytocin levels of amniotic fluid, these peptides were measured under conditions (1) in which the fetus lacks vasopressin (Brattleboro strain) and (2) where high maternal oxytocin and vasopressin plasma levels were induced by means of a controlled-delivery Accurel-collodion device. No vasopressin could be demonstrated in amniotic fluid of vasopressin-deficient fetuses present in a heterozygous (i.e., vasopressin-synthetizing mother). High peptide levels on the maternal side of Wistar rats generally failed to affect the amniotic fluid levels. The increase that was occasionally seen in amniotic vasopressin was probably due to fetal release concomitant with growth retardation. Amniotic vasopressin is derived from the fetus. Since amniotic fluid oxytocin is neither derived from the mother nor from the fetal brain, other fetal sources should be considered.

Topics: Amniotic Fluid; Animals; Arginine Vasopressin; Body Weight; Brain; Female; Fetus; Maternal-Fetal Exchange; Organ Size; Oxytocin; Peptides; Placenta; Pregnancy; Rats; Rats, Brattleboro; Rats, Inbred Strains

Arginine-vasopressin (AVP) and oxytocin are neuropeptides that are not only released as hormones into the peripheral circulation, but are also involved in central processes, e.g., in brain development. Earlier experiments suggested an inverse relationship between amniotic AVP and fetal growth. To see whether increased peptide levels reflect fetal growth retardation, and to determine cause and effect of this relationship, AVP and oxytocin content were determined in amniotic fluid of growth-retarded fetuses by radioimmunoassay. Growth retardation was established either by intraperitoneal administration of methylazoxymethanol to the mother, or by undernourishment of the mother. Elevated amniotic AVP levels were found in the methylazoxymethanol-treated and undernourished rats, partly concomitant with smaller amount of amniotic fluid. Amniotic AVP levels were inversely related to fetal body weight, while a similar trend was found for fetal brain weight. In addition, a positive correlation was found between fetal body weight and amniotic oxytocin in control rats.

Topics: Amniotic Fluid; Animals; Arginine Vasopressin; Body Weight; Female; Fetal Growth Retardation; Fetus; Oxytocin; Peptides; Pregnancy; Rats; Rats, Inbred Strains

The origin of endogenous opioid peptides that inhibit release of vasopressin (VP) and oxytocin (OT) into the bloodstream after tail electroshock was investigated. We hypothesized that endogenous opioid peptides derived from the anterior pituitary reduced secretion of VP and OT during this stimulus. To test this hypothesis, dexamethasone (DEX) was used to preferentially suppress release of endorphins with ACTH from the anterior pituitary. We evaluated the effects of an opiate receptor antagonist, naltrexone, on the rise in plasma [VP] and [OT] after tail electroshock in male Sprague-Dawley rats given DEX either chronically or acutely before the shock. In the chronic study rats were injected SC daily with saline (3.2 ml/kg) or DEX (0.2 mg/kg) for 17 days. In the short term study, rats were injected IP with saline (5 ml/kg) or DEX (0.5 mg/kg) the day before and again 105 min prior to tail electroshock. Thirty min (chronic study) or 90 min (acute study) after saline or DEX was given on the last day, rats were injected SC with saline (1 ml/kg) or naltrexone (1 mg/kg). Fifteen min later, animals received tail electroshock (41 V, 30 sec) and were decapitated 15 sec after shock was completed. Control animals were treated similarly but not shocked. Amounts of VP and OT in plasma and the neurointermediate lobe were quantified by RIA. [VP] and [OT] were elevated in plasma of all rats given tail electroshock. Greater increases (p less than 0.05) in hormone concentrations were measured in plasma of shocked rats treated with DEX.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Dexamethasone; Electroshock; Hematocrit; Male; Naltrexone; Oxytocin; Pituitary Gland; Rats; Rats, Inbred Strains; Tail; Time Factors; Vasopressins

The role of the cervix in labor induction has been studied in a previous report. Cervical preparation by mechanical methods did not alter the course of induced labor. The same hypothesis is further elucidated in the present study using prostaglandin E2 vaginal suppositories for cervical preparation. Forty-seven pregnant women near term with Bishop scores of 4 or less were divided into three study groups: control subjects, oxytocin-treated patients, and prostaglandin group. A 12-hour preparation phase procedure was carried out to produce cervical and/or myometrial changes. All women had continuous measurement of uterine activity by an extraovular catheter. At the end of the preparation phase, the Bishop score was reevaluated, amniotomy carried out in all patients, and oxytocin infusion either started or continued. Although prostaglandin and oxytocin both significantly changed the cervix, oxytocin had the shortest induction-to-delivery interval, though the prostaglandin-treated group required lower concentrations of oxytocin. The authors conclude that with rigid control of Bishop score and timing of amniotomy and oxytocin infusion rates, prostaglandin-induced cervical changes alone did not uniquely benefit labor induction in the doses used, or within the time frame of the study.

Topics: Adult; Body Weight; Cervix Uteri; Cesarean Section; Dinoprostone; Female; Gestational Age; Humans; Labor, Induced; Maternal Age; Oxytocin; Pregnancy; Prostaglandins E; Prostaglandins E, Synthetic

Magnocellular neurons in the supraoptic and paraventricular nuclei synthesize and release vasopressin and oxytocin in response to dehydration. Pinealectomy has been observed to decrease the distribution in the supraoptic nuclei of thiamine diphosphate-phosphohydrolase, an enzyme specific for the Golgi apparatus that correlates positively with neurosecretory activity. Based upon these studies we postulated that pinealectomy would alter the concentration of neurohypohysial hormones in plasma elevated by 48 hr of water deprivation. In addition, we investigated the possibility that pinealectomy would affect vasopressin concentration in another circumventricular organ, the subfornical organ (SFO) and in a adjacent fiber tract of the limbic system, the hippocampal commissure-fornix (HC-F). Adult, male, Sprague-Dawley rats exposed to a 12 hr light/dark cycle were either unoperated (controls; C), sham-operated (Sham; S) or pinealectomized (PX) three weeks prior to testing. Food and water consumption and urinary excretion of Na and K were measured for 7 days. On the fifth day, half of the animals in each treatment group (C, S, PX) were deprived of water for 48 hr. Animals were decapitated on day 8. Vasopressin and oxytocin in plasma were extracted using bentonite and acetone-ether, respectively, then quantified by radioimmunoassay. The SFO and HC-F were microdissected from each brain. Like tissues from 4 rats were pooled, homogenized in 0.1 N HCl, and centrifuged. The supernatant was neutralized and vasopressin was quantified by radioimmunoassay. Dehydration resulted in antidiuresis, increased urine concentrations of Na and K, a decreased ratio of Na:K in urine, and reduced food consumption of similar magnitudes in all groups (C, S, PX; p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Dehydration; Eating; Hematocrit; Hippocampus; Light; Male; Neurosecretory Systems; Oxytocin; Pineal Gland; Rats; Rats, Inbred Strains; Subfornical Organ; Time Factors; Vasopressins

Experiments were undertaken to determine the role of the septum on the afferent control of the milk ejection reflex in lactating rats. Massive septal lesions were produced by passing radio-frequency current through lesioning electrodes. Intramammary pressure recordings during suckling showed no significant alterations either in the frequency of milk ejections or in their amplitude and time course. Electrophysiological recordings of identified oxytocin-secreting neurones in supraoptic nuclei of septal-lesioned rats engaged in suckling showed that the pattern of background electrical activity and of the high frequency discharges at milk ejection were normal. The weight of litters from rats lesioned on the third day post-partum increased in a way parallel to that of control litters up to the fifteenth post-natal day. Electrical stimulation was applied bilaterally to the lateral septum in trains of long duration (20-55 min) at varying frequencies. Frequencies of 5 and 10 Hz interrupted the reflex during the period of stimulation. At 1 Hz, milk ejections were not interrupted but the intervals between successive milk ejections were significantly increased in comparison to the intervals before stimulation. Electrical stimulation applied to the septum in short trains of 1 or 3 min at 5 and 10 Hz significantly delayed the appearance of the subsequent milk ejection. At 1 Hz, no effect was observed. Septal stimulation at 1 Hz for 20 min or more did not significantly alter the electrocorticogram during the period of stimulation. Stimulation at 5 Hz for the same period of time always desynchronized the e.e.g. for several minutes after the cessation of stimulation. It is concluded that the septum is not essential for the onset and the maintenance of reflex milk ejections during lactation. The results suggest, however, that in the normal non-anaesthetized animal, septal activation could modulate the frequency of milk ejections.

Topics: Action Potentials; Animals; Body Weight; Electric Stimulation; Female; Lactation; Mammary Glands, Animal; Milk Ejection; Oxytocin; Pregnancy; Pressure; Rats; Septum Pellucidum; Supraoptic Nucleus; Time Factors

Topics: Animals; Body Weight; Female; Lactation; Mammary Glands, Animal; Milk Ejection; Oxytocin; Pregnancy; Rats; Rats, Inbred Strains; Starvation

Ten healthy lactating sows were given single IV injections of 5 to 10 IU of oxytocin and single IV or IM injections of 0.2 to 0.6 mg of deamino-1-monocarba-(2-O-methyltyrosine)-oxytocin [d(COMOT)]. Studies were done with d(COMOT) concerning the dose-response relationship, the influence of the lactation stage on the duration of the milk let-down effect, and the difference between the IV and IM injections. The mean duration of response was 14 minutes for oxytocin and 6.2 hours for d(COMOT). Intramammary pressure was also measured in 3 sows, using 10 IU of oxytocin IV or 0.6 mg of d(COMOT) IV. Oxytocin resulted in a strong initial increase of the intramammary pressure for about 7 minutes. The d(COMOT) caused the same initial response, followed by secondary oscillations lasting for at least 4 hours.

Topics: Animals; Body Weight; Female; Lactation; Lactation Disorders; Mammary Glands, Animal; Oxytocics; Oxytocin; Pregnancy; Pressure; Swine; Swine Diseases

The oxytocin (OT) content of pituitary glands from neonatal rats was reduced by parturition, indicating possible release from fetal glands during labor. The content of fetal glands fell from 2.5 ng/gland in utero to 1 ng/gland immediately after birth. Rabbit serum antibodies against OT were administered to pregnant or fetal rats preceding parturition or to lactating rats on Day 10 of lactation. Antibody administration to lactating rats resulted in a decrease in weight gain of suckling pups, indicating that OT was bound by antibody. Administration of OT antibody to pregnant rats had no effect on the duration of gestation while injection into fetal pups resulted in an 18 h increase in the mean duration of gestation compared to sham-injected controls. These studies indicate that fetal OT might have a role in initiating parturition in the rat.

Topics: Animals; Animals, Newborn; Body Weight; Female; Fetus; Gestational Age; Immune Sera; Labor, Obstetric; Lactation; Oxytocin; Pituitary Gland; Pregnancy; Rats; Rats, Inbred Strains

A prospective study was conducted in a level II maternity unit to investigate the incidence of hyperbilirubinemia in healthy, term, breast-fed and formula-fed infants. Serum bilirubin levels were determined for 176 breast-red and 164 formula-fed infants in cord blood and on days 1, 2, 3 and 5 after birth. The mean total bilirubin levels were significantly higher on each postnatal day in the breast-fed infants, as was the proportion of infants with peak levels above 12 mg/dl (205 mumol/l; 28% v. 6%). The breast-fed infants also had significantly higher proportional weight losses on each postnatal day than the formula-fed infants. However, there was no correlation between the cumulative weight loss on day 3 and bilirubin levels on the same day with either feeding regimen. None of the infants required an exchange transfusion or prolonged care in hospital for hyperbilirubinemia.

Topics: Bilirubin; Body Weight; Breast Feeding; Female; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Jaundice, Neonatal; Oxytocin; Pregnancy; Prospective Studies

The release of oxytocin and neurophysin during suckling has been studied in conscious unrestrained guinea-pigs. After prior separation, mothers and litters were allowed to suckle for a period of 10 min, and the weight gain of the litter recorded as an index of milk transfer. Maternal blood samples were obtained without disturbance through previously implanted intravenous cannulae and neurophysin and oxytocin determined on unextracted plasma by specific and sensitive radioimmunoassays. In 82 out of 118 experiments the young gained weight during suckling (1.6 +/- 0.1 (S.E.M.) g/pup) and this was associated with large rises in both oxytocin and neurophysin concentrations in plasma (mean concentrations: oxytocin 65.4 fmol/ml, neurophysin 360 fmol/ml). Where serial samples were taken, oxytocin and neurophysin showed a rapid rise and fall in concentration closely associated with the occurrence of milk ejection as judged by the behaviour of the litter. The present results provide the first direct evidence of a spurt release of both oxytocin and neurophysin measured simultaneously during milk ejection. The conscious lactating guinea-pig thus provides a useful laboratory model in which to study hormone release during milk ejection.

Topics: Animals; Body Weight; Female; Guinea Pigs; Lactation; Male; Milk Ejection; Neurophysins; Oxytocin; Pregnancy

Lactating guinea-pigs were passively immunized with an antiserum to oxytocin of high titre, specificity and avidity. Single i.v. injections of 0.1-0.4 ml antiserum produced high titres which decayed slowly (half-life congruent to 7 days). Passively administered antiserum was effective in vivo; the clearance of exogenous oxytocin from plasma was greatly slowed in immunized animals. Passive immunization with 0.4 ml antiserum reduced milk transfer to the litter during suckling episodes of 10 min, and overall litter growth rates were significantly decreased. Non-immune serum was without effect. Plasma neurophysin levels showed the same large rises during suckling in immunized animals, indicating that neurohypophysial activation was unimpaired. Despite the presence of high titres of antiserum, some milk transfer still occurred at milk ejection. In-vitro experiments showed that more than 25% of oxytocin remained free 20s after mixing with plasma taken from passively immunized animals. It is probable that the antiserum in the circulation was unable to bind all the oxytocin released from the posterior pituitary gland before it reached the mammary gland.

Topics: Animals; Body Weight; Female; Guinea Pigs; Immunization, Passive; Lactation; Milk Ejection; Neurophysins; Oxytocin; Pregnancy

Topics: Ambystoma; Animals; Body Weight; Gills; Metamorphosis, Biological; Oxytocin; Prolactin; Tail; Thyroxine; Water-Electrolyte Balance

Topics: Animals; Arginine Vasopressin; Body Weight; Carboxy-Lyases; Dehydration; Hematocrit; Kidney; Male; Mice; Mice, Inbred Strains; Ornithine Decarboxylase; Osmolar Concentration; Oxytocin; Time Factors; Water Deprivation

Concentrations of plasma angiotensin II (AII) have been measured in the second stage of labour or before delivery by elective Caesarean section in 134 women and some factors influencing the levels have been assessed. Plasma AII concentrations in the second stage of labour were higher than levels previously observed before the onset of labour in both primigravid and multiparous women. Markedly lower levels were found following delivery by elective Caesarean section than following vaginal delivery. Multiparae had higher AII concentrations than primigravidae both before the onset of labour and at delivery. Epidural analgesia was associated with significantly lower AII concentrations; in primigravidae receiving such analgesia a statistically significant relation was found between AII concentration and diastolic blood pressure at delivery. A similar relation was found in the nonproteinuric patients delivered by Caesarean section. The estimated duration of the second stage of labour was the major factor affecting AII concentration in normal multiparae. In both primigravid and multiparous women, AII concentrations were markedly raised in association with proteinuria.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Angiotensin II; Blood Pressure; Body Weight; Cesarean Section; Female; Humans; Labor, Obstetric; Maternal Age; Oxytocin; Parity; Pregnancy; Pregnancy Complications; Proteinuria; Time Factors

Plasma bilirubin was estimated on 690 term infants on about the 6th day of life. Perinatal factors were recorded and the results analysed. Hyperbilirubinaemia was defined as a level greater than 205 micromol/1 (12 mg/100 ml) and this was present in 20% of cases. Three factors--epidural analgesia, breast feeding, and poor weight recovery--showed highly significant associations with jaundice. The relative importance of these is discussed and compared with recent reports. Induction of labour, for reasons other than postmaturity, and a gestational age less than 39 weeks showed a slightly increased incidence of jaundice. There was no correlation with other factors tested including oxytocic drug administration. Despite the high incidence (20%) of hyperbilirubinaemia, only 2.5% infants needed treatment and none required exchange transfusion. Radical changes in obstetric management or infant feeding are not indicated.

Topics: Anesthesia, Epidural; Body Weight; Breast Feeding; Female; Gestational Age; Humans; Infant, Newborn; Jaundice, Neonatal; Labor, Induced; Oxytocin; Pregnancy; Prospective Studies

Lesions of the median raphe (MR) nucleus were placed in cycling female rats and their ability to lactate was evaluated following subsequent pregnancies. Pups from MR-lesioned (MRL) animals grew more slowly and had greatly impaired survival rates compared to pups from sham-lesioned animals. Chronic treatment of MRL mothers with oxytocin (Oxy; 1 IU, s.c., once or twice/day) did not increase the growth rates of their litters. Acute responses to exogenous Oxy (1 IU, i.p.) in MRL mothers, measured by the weight gain of litters during 1/2-h suckling intervals before and after injection, were marginally significant. Milk yield during the total hour suckling period (stomach contents of pups) was clearly less in the MRL animals (p less than 0.01). Treatment with either prolactin (Prl; 250 microgram, twice/day), Prl + GTC (4 mg/kg gorwth hormore, 30 microgram/kg thyroxine, 0.5 mg/rat cortisol, once/day), or 5-HTP (75 mg 5-hydroxytryptophan/kg, twice/day) did not improve the growth rates of litters from MRL animals. However, when milk yield (stomach contents after 1 h) following a 14-h non-suckling interval was measured, lactogenic hormones (Prl or Prl + GTC) restored milk yield in MRL animals to control levels. This response was clearly not dependent upon exogenous Oxy. These results suggest that deficits in the release of lactogenic hormones are involved in the impairments in lactation following lesions of the MR nucleus.

Topics: Animals; Animals, Newborn; Body Weight; Brain Stem; Estrus; Female; Lactation; Milk; Oxytocin; Pregnancy; Raphe Nuclei; Rats

The stimulating effect of different pituitary hormones on longitudinal bone growth was determined with tetracycline as intravital marker in hypophysectomized rats. Growth hormone was found to be the most effective growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating activity. TSH exerts its effect via the production of thyroxine, whereas the growth stimulation by prolactin seems to be a direct effect of this hormone, similar to the effect of growth hormone. The LH, FSH, ACTH, MSH, vasopressin and oxytocin preparations did not stimulate longitudinal bone growth.

Topics: Adrenocorticotropic Hormone; Animals; Body Weight; Bone Development; Cartilage; Drug Synergism; Female; Follicle Stimulating Hormone; Growth Hormone; Hypophysectomy; Luteinizing Hormone; Melanocyte-Stimulating Hormones; Oxytocin; Pituitary Hormones; Prolactin; Rats; Stimulation, Chemical; Thyrotropin; Thyroxine; Tibia; Vasopressins

Lyophilized bovine, porcine, and human choroid plexuses contain .02-.09 U of antidiuretic activity per milligram. The antidiuretic factor in bovine choroid plexus was concentrated 100 times by extraction with acetic acid, fractional precipitation with acetone and ethyl ether, gel filtration, and paper chromatography. Resulting choroid plexus fraction IIgammaB2 was eluted from Sephadex G-25 in position corresponding to molecular weight between 750 and 3,500; its antidiuretic activity was destroyed by trypsin, performic acid, and thioglycollic acid, but was not affected by leucine aminopeptidase, carboxypeptidase A or B, or cyanogen bromide. HgammaB2 possesses antidiuretic, pressor, and oxytocic potencies (measured in anesthetized-hydrated rat, anesthetized rat, and isolated rat uterus, respectively) of 1.9, 0.5, and 0.1 U/mg, respectively.

Topics: Aminopeptidases; Animals; Biological Assay; Body Weight; Bufo marinus; Carboxypeptidases; Cattle; Choroid Plexus; Cyanogen Bromide; Dogs; Formates; Haplorhini; Humans; Lipid Metabolism; Oxytocin; Pituitary Gland; Rats; Swine; Thioglycolates; Trypsin; Vasopressins

Topics: Analgesia; Animals; Arginine Vasopressin; Body Temperature; Body Weight; Drug Synergism; Female; Humans; Morphine Dependence; Naloxone; Oligopeptides; Oxytocin; Rats; Structure-Activity Relationship; Vasopressins

Topics: Animals; Body Weight; Ergolines; Feeding Behavior; Female; Hydrocortisone; Lactation; Mammary Glands, Animal; Oxytocin; Pregnancy; Prolactin; Rats

Topics: Animals; Body Weight; Depression, Chemical; Female; Lactation; Oxytocin; Pregnancy; Prostaglandin Antagonists; Prostaglandins; Rats; Time Factors

Topics: Animals; Body Weight; Female; Injections, Subcutaneous; Lactation; Male; Mammary Glands, Animal; Milk; Oxytocin; Pituitary Gland; Pituitary-Adrenal System; Pregnancy; Prolactin; Propranolol; Rabbits; Sympathetic Nervous System; Time Factors

Topics: Animals; Animals, Newborn; Behavior, Animal; Body Weight; Breast Feeding; Feeding Behavior; Female; Food Deprivation; Hunger; Lactation; Male; Mammary Glands, Animal; Muscle Contraction; Oxytocin; Pregnancy; Rats; Reaction Time; Satiation; Sucking Behavior

Topics: Body Weight; Breast; Breast Feeding; Female; Humans; Lactation; Milk, Human; Oxytocin; Pressure; Reflex; Sucking Behavior; Time Factors

Topics: Administration, Oral; Animals; Body Weight; Drug Synergism; Ergolines; Female; Lactation; Lethal Dose 50; Lisuride; Oxytocin; Pregnancy; Prolactin; Urea

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Body Weight; Corticosterone; Cortisone; Desoxycorticosterone; Estradiol; Female; Gonads; Growth Hormone; Male; Oxygen Consumption; Oxytocin; Pancreas; Parathyroid Glands; Pineal Gland; Pituitary Gland; Progesterone; Prolactin; Rats; Testosterone; Thymus Gland; Thyroid Gland; Thyroxine; Triiodothyronine; Vasopressins

Topics: Animals; Body Weight; Female; Lactation; Mammary Glands, Animal; Oxytocin; Pregnancy; Prolactin; Rats; Secretory Rate; Time Factors

Using Csapo's technique, a single dose of 24.3 +or- 1.1 mg prostaglandin F2alpha (PGF2alpha) had been delivered intraamniotically to 20 sedated pregnant patients (15.9 +or- 0.6 weeks pregnant) in order to provoke a PG impact (PGI), a consequent progesterone (P) withdrawal, and a conversion of the pharmacologically refractory normal pregnant uterus into a reactive organ. The side effects were occasional and acceptable and no further PGF2alpha treatment was needed except in 4 cases (5-10 mg). Only after the Oxytocin test showed that the uterus is becoming reactive, was 50 mU/minute oxytocin infused intravenously to facilitate the evolution of IUP to 93 +or- 3 mmHg and thus promote clinical progress. All the 20 patients aborted both the fetus and the placenta in 16.5 +or- 2.1 hours, but 8 women retained small placental residues to be removed by curettage. The Csapo score was a high 92 +or- 2. As early as 3 hours after PGI, the plasma P levels already decreased significantly. They continued to decline throughout the IAT and reached a 72% withdrawal when the fetus was aborted. 15 patients whose P withdrawal was rapid, aborted before the mean IAT, while those 5 women whose P withdrawal was slow aborted after this time. Thus, the rate of P withdrawal was direct while parity and gestational age indirectly related to the IAT. Studies are in progress to elucidate further the abortifacient action of PGF2alpha and through this knowledge promote predictable therapy.

Topics: Abortion, Induced; Adolescent; Adult; Amniotic Fluid; Body Height; Body Weight; Curettage; Female; Fetus; Gestational Age; Humans; Injections; Muscle Contraction; Nausea; Oxytocin; Parity; Pregnancy; Pressure; Progesterone; Prostaglandins; Time Factors; Uterus; Vomiting

Topics: Age Factors; Animals; Body Composition; Body Weight; Extraembryonic Membranes; Female; Fetus; Lactation; Male; Milk; Oxytocin; Pregnancy; Regression Analysis; Sheep; Sulfur; Uterus; Wool

Topics: Animals; Body Weight; Electrophoresis, Polyacrylamide Gel; Environment, Controlled; Female; Lactation; Mammary Glands, Animal; Milk; Oxytocin; Phentolamine; Pituitary Gland; Pregnancy; Prolactin; Rats; Stimulation, Chemical; Sucking Behavior; Time Factors; Weaning

Topics: Animals; Body Weight; Delayed-Action Preparations; Depression, Chemical; Dose-Response Relationship, Drug; Estradiol; Female; Lactation; Mammary Glands, Animal; Norethindrone; Oxytocin; Pregnancy; Pressure; Progesterone; Rats; Time Factors

Topics: Aldosterone; Animals; Body Weight; Female; Injections, Intravenous; Natriuresis; Oxytocin; Potassium; Prolactin; Sheep; Sodium Chloride; Water-Electrolyte Balance

Topics: Body Weight; Female; Gestational Age; Humans; Labor, Induced; Oxytocin; Parity; Pregnancy; Prostaglandins

Topics: Anesthesia, General; Anesthesia, Obstetrical; Apgar Score; Body Weight; California; Cesarean Section; Extraction, Obstetrical; Extraembryonic Membranes; Female; Fetal Death; Fetus; Humans; Infant Mortality; Labor Presentation; Labor, Induced; Obstetric Labor Complications; Oxytocin; Parity; Pelvimetry; Pregnancy; Rupture

Topics: Animals; Antibodies; Binding Sites; Body Weight; Delivery, Obstetric; Female; Immune Sera; Injections, Intraperitoneal; Iodine Isotopes; Lactation; Oxytocin; Pregnancy; Rabbits; Rats

Topics: Animals; Animals, Newborn; Body Weight; Female; Lactation; Mammary Glands, Animal; Mice; Oxytocin; Pregnancy

Topics: Animals; Animals, Newborn; Body Weight; DNA; Female; Growth Hormone; Hydrocortisone; Lactation; Mammary Glands, Animal; Organ Size; Oxytocin; Pregnancy; Prolactin; Rats; RNA

Topics: Animals; Body Weight; Depression, Chemical; Estrogens; Female; Lactation; Mammary Glands, Animal; Milk; Oxytocin; Pregnancy; Rats

Topics: Animals; Body Weight; Female; Hydrocortisone; Hypothalamus; Lactation Disorders; Male; Organ Size; Oxytocin; Pregnancy; Prolactin; Rats

Topics: Animals; Animals, Newborn; Body Weight; Chlorobutanol; Depression, Chemical; Female; Humans; Lactation; Mice; Milk; Oxytocin; Pregnancy

Topics: 17-Ketosteroids; Aldosterone; Blood Volume; Body Weight; Feces; Humans; Hydrocortisone; Male; Natriuresis; Oxytocin; Renin; Sodium; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Topics: Animals; Animals, Newborn; Body Weight; Depression, Chemical; Female; Glucose; Hypothalamo-Hypophyseal System; Lactation; Lactose; Mammary Glands, Animal; Milk; Oxytocin; Pregnancy; Prolactin; Rats; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Autopsy; Body Weight; Female; Fetus; Hypophysectomy; Kidney; Lactation; Mammary Glands, Animal; Organ Size; Ovary; Oxytocin; Pituitary Gland; Pregnancy; Rats; Spleen; Time Factors; Transplantation, Heterologous; Uterus

Topics: Animals; Behavior, Animal; Body Weight; Drinking; Eating; Female; Growth; Injections, Intravenous; Injections, Subcutaneous; Lactation; Mammary Glands, Animal; Mice; Oxytocin; Pregnancy; Time Factors

Topics: Animals; Arginine; Body Weight; Estrone; Female; Light; Lizards; Muscle Contraction; Organ Size; Oviducts; Oxytocin; Peptides; Periodicity; Pituitary Hormones, Posterior; Progesterone; Temperature; Time Factors; Vasotocin

1. The effect of bilateral lesions in the anterior hypothalamus on the histology and content of melanocyte-stimulating hormone (MSH) of the pars intermedia has been studied in the adult male rat.2. By 7-15 days striking histological changes, suggestive of hyperactivity, were evident. These changes were accompanied by an elevated MSH content, which was particularly noticeable at 7 days.3. By 7 days there was an increase in the acid phosphatase activity of pars intermedia cells, as demonstrated histochemically.4. It was concluded that a hypothalamic control system exists for the mammalian pars intermedia and may involve both inhibitory and excitatory components.

Topics: Acid Phosphatase; Animals; Body Weight; Electric Injuries; Hypothalamus; Male; Melanocyte-Stimulating Hormones; Oxytocin; Pituitary Gland; Rats; Vasopressins

Topics: Animals; Blood Chemical Analysis; Body Weight; Dehydration; Hematocrit; Male; Osmolar Concentration; Oxytocin; Pituitary Gland; Rats; Vasopressins

Topics: Animals; Animals, Newborn; Body Weight; Female; Hydrazines; Injections, Intramuscular; Lactation; Milk; Oxytocin; Pregnancy; Swine; Thiocarbamates

Topics: Amniotic Fluid; Bilirubin; Body Weight; Colposcopy; Cytodiagnosis; Delivery, Obstetric; Diagnosis, Differential; Fasting; Female; Germany, East; Humans; Infant Mortality; Infant, Newborn; Infant, Newborn, Diseases; Labor, Induced; Oxytocin; Placenta; Pregnancy; Pregnancy Complications; Pregnancy, Prolonged; Statistics as Topic; Uterus; Vaginal Smears

Topics: Animals; Body Weight; Female; Hypothalamo-Hypophyseal System; Hypothalamus; Lactation; Oxytocin; Pregnancy; Rats

Topics: Animals; Animals, Newborn; Body Weight; Estrogens; Estrus; Female; In Vitro Techniques; Muscle Contraction; Organ Size; Ovary; Oxytocin; Pregnancy; Rats; Testosterone; Uterus; Vaginal Smears

Topics: Animals; Body Weight; Cordotomy; Female; Food; Lactation; Mammary Glands, Animal; Milk; Oxytocin; Pregnancy; Prolactin; Rats; Water

Topics: Animals; Animals, Newborn; Body Weight; Female; Lactation; Oxytocin; Pregnancy; Rats

Topics: Animals; Anura; Body Weight; Oxytocin; Pituitary Hormones, Posterior; Sodium; Water-Electrolyte Balance

Topics: Animals; Appetite; Body Weight; Endocrinology; Female; Humans; Hydrazines; Hypothalamus; Lactation; Mammary Glands, Animal; Oxytocin; Pharmacology; Prolactin; Rats; Reproduction; Research; Thirst

Topics: Amphibians; Animals; Anura; Biological Evolution; Biological Transport; Body Weight; Chordata; Endocrinology; Fishes; Oxytocin; Pharmacology; Phylogeny; Physiology, Comparative; Pituitary Hormones, Posterior; Research; Sharks; Sodium; Vasopressins; Vasotocin; Vertebrates; Water; Water-Electrolyte Balance

Topics: Animals; Body Weight; Glomerular Filtration Rate; Oxytocin; Pituitary Hormones, Posterior; Sodium; Urine; Urodela; Vasotocin; Water-Electrolyte Balance

Topics: Acetylcholine; Adrenal Glands; Body Weight; Estrone; Female; Humans; Oxytocin; Pharmacology; Rats; Research; Thyroidectomy; Thyroxine; Uterus

Topics: Animals; Animals, Newborn; Body Weight; Brain; Cerebral Cortex; Cortical Spreading Depression; Depression; Female; Humans; Lactation; Oxytocin; Pain; Pharmacology; Physiology; Potassium Chloride; Rats; Research; Reticular Formation; Stress, Physiological

The action of certain substances on the release of oxytocin has been studied in unanaesthetized lactating rats. The release of oxytocin has been assessed by the increase in weight after suckling of rats separated overnight from the mother. A large variety of substances appear to block the release of oxytocin. These include pentolinium, atropine and chlorpromazine. Adrenaline and noradrenaline also cause a block in the release of oxytocin, and it is suggested that adrenaline blocks the central release of oxytocin as well as blocking its peripheral action. Reserpine and oestradiol in the doses administered did not block the release of oxytocin. Block also occurred after the ingestion of water, ethanol and normal saline, an effect which may be produced indirectly by impulses from the gastro-intestinal tract.

Topics: Animals; Body Weight; Breast Feeding; Ethanol; Female; Humans; Lactation; Oxytocics; Oxytocin; Pituitary Gland; Pituitary Gland, Posterior; Rats; Reserpine