pituitrin and Stress-Disorders--Post-Traumatic

The motivation to engage in social behaviors is influenced by past experience and internal state, but also depends on the behavior of other animals. Across species, the oxytocin (Oxt) and vasopressin (Avp) systems have consistently been linked to the modulation of motivated social behaviors. However, how they interact with other systems, such as the mesolimbic dopamine system, remains understudied. Further, while the neurobiological mechanisms that regulate prosocial/cooperative behaviors have been extensively examined, far less is understood about competitive behaviors, particularly in females. In this chapter, we highlight the specific contributions of Oxt and Avp to several cooperative and competitive behaviors and discuss their relevance to the concept of social motivation across species, including humans. Further, we discuss the implications for neuropsychiatric diseases and suggest future areas of investigation.

Topics: Aggression; Animals; Autism Spectrum Disorder; Behavior, Animal; Brain; Competitive Behavior; Cooperative Behavior; Dopamine; Female; Humans; Mental Disorders; Motivation; Oxytocin; Pair Bond; Personality Disorders; Schizophrenia; Schizophrenic Psychology; Social Behavior; Stress Disorders, Post-Traumatic; Vasopressins

Animal studies point to the role of two neuropeptides-oxytocin and vasopressin-in the regulation of affiliative behaviors including mating, pair-bond formation, maternal/parenting behavior, and attachment. These findings may have important implications for understanding and treating clinical disorders marked by social deficits and/or disrupted attachment. This review focuses on advances made to date in the effort to forge links between basic and clinical research in the area of neuropeptides and social behavior. The literature on oxytocin and its involvement in stress response, affiliation, and prosocial behavior is reviewed, and the implications of these findings for such disorders as autism as well as other social and stress-related disorders including social phobia, post-traumatic stress disorder, and some personality disorders are considered. Finally, unresolved issues and directions for future research are discussed.

Topics: Animals; Autistic Disorder; Humans; Oxytocin; Personality Disorders; Phobic Disorders; Social Behavior; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

Posttraumatic stress disorder (PTSD) is characterized by a peculiar cognitive state. The traumatic event(s) are partly hypermemorized, partly blurred, whereas the ability to store and retrieve new information is impaired. The question is raised as to what the biological systems might be that 'carry' this cognitive paradox. Four possible candidate systems are discussed. It is concluded that understimulation of the corticosteroid receptors, particularly the glucocorticoid receptors (GRs), overactivity of the noradrenaline (NA) and vasopressin (VA) systems, and deficits in the 5-Hydroxytryptamine (5-HT) system, particularly the 5-HT(1A) system, could generate a cognitive syndrome similar to the one observed in PTSD. A dual hypothesis is launched holding that (a) in PTSD, downregulation of the 5-HT(1A) receptor system is the primary lesion, while the other dysfunctions mentioned are subsidiaries and that (b) underdevelopment of or damage to the 5-HT(1A) receptor system will make a person PTSD-prone.

Topics: Animals; Cognition; Cognition Disorders; Humans; Models, Biological; Norepinephrine; Receptor, Serotonin, 5-HT1A; Receptors, Steroid; Serotonin; Stress Disorders, Post-Traumatic; Vasopressins

Topics: Aggression; Animals; Neuroendocrinology; Oxytocin; Stress Disorders, Post-Traumatic; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Arousal; Humans; Memory; Mental Recall; Receptors, Adrenergic; Stress Disorders, Post-Traumatic; Vasopressins

Military-related post-traumatic stress (PTS) is associated with numerous symptom clusters and diminished autonomic cardiovascular regulation. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®) is a noninvasive, closed-loop, allostatic, acoustic stimulation neurotechnology that produces real-time translation of dominant brain frequencies into audible tones of variable pitch and timing to support the auto-calibration of neural oscillations. We report clinical, autonomic, and functional effects after the use of HIRREM® for symptoms of military-related PTS.. Eighteen service members or recent veterans (15 active-duty, 3 veterans, most from special operations, 1 female), with a mean age of 40.9 (SD = 6.9) years and symptoms of PTS lasting from 1 to 25 years, undertook 19.5 (SD = 1.1) sessions over 12 days. Inventories for symptoms of PTS (Posttraumatic Stress Disorder Checklist - Military version, PCL-M), insomnia (Insomnia Severity Index, ISI), depression (Center for Epidemiologic Studies Depression Scale, CES-D), and anxiety (Generalized Anxiety Disorder 7-item scale, GAD-7) were collected before (Visit 1, V1), immediately after (Visit 2, V2), and at 1 month (Visit 3, V3), 3 (Visit 4, V4), and 6 (Visit 5, V5) months after intervention completion. Other measures only taken at V1 and V2 included blood pressure and heart rate recordings to analyze heart rate variability (HRV) and baroreflex sensitivity (BRS), functional performance (reaction and grip strength) testing, blood and saliva for biomarkers of stress and inflammation, and blood for epigenetic testing. Paired t-tests, Wilcoxon signed-rank tests, and a repeated-measures ANOVA were performed.. Clinically relevant, significant reductions in all symptom scores were observed at V2, with durability through V5. There were significant improvements in multiple measures of HRV and BRS [Standard deviation of the normal beat to normal beat interval (SDNN), root mean square of the successive differences (rMSSD), high frequency (HF), low frequency (LF), and total power, HF alpha, sequence all, and systolic, diastolic and mean arterial pressure] as well as reaction testing. Trends were seen for improved grip strength and a reduction in C-Reactive Protein (CRP), Angiotensin II to Angiotensin 1-7 ratio and Interleukin-10, with no change in DNA n-methylation. There were no dropouts or adverse events reported.. Service members or veterans showed reductions in symptomatology of PTS, insomnia, depressive mood, and anxiety that were durable through 6 months after the use of a closed-loop allostatic neurotechnology for the auto-calibration of neural oscillations. This study is the first to report increased HRV or BRS after the use of an intervention for service members or veterans with PTS. Ongoing investigations are strongly warranted.. NCT03230890 , retrospectively registered July 25, 2017.

Topics: Adult; Allostasis; Angiotensin I; Angiotensin II; Biomarkers; C-Reactive Protein; Electroencephalography; Epinephrine; Heart Rate; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Male; Middle Aged; Military Personnel; Monitoring, Physiologic; Norepinephrine; North Carolina; Peptide Fragments; Pilot Projects; Self Report; Stress Disorders, Post-Traumatic; Vasopressins; Veterans

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with a wide range of behavioral disturbances and serious consequences for both patient and society. One of the main reasons for unsuccessful therapies is insufficient knowledge about its underlying pathomechanism. In the search for centrally signaling molecules that might be relevant to the development of PTSD we focus here on arginine vasopressin (AVP). So far AVP has not been strongly implicated in PTSD, but different lines of evidence suggest a possible impact of its signaling in all clusters of PTSD symptomatology. More specifically, in laboratory rodents, AVP agonists affect behavior in a PTSD-like manner, while significant reduction of AVP signaling in the brain e.g. in AVP-deficient Brattleboro rats, ameliorated defined behavioral parameters that can be linked to PTSD symptoms. Different animal models of PTSD also show alterations in the AVP signaling in distinct brain areas. However, pharmacological treatment targeting central AVP receptors via systemic routes is hampered by possible side effects that are linked to the peripheral action of AVP as a hormone. Indeed, the V1a receptor, the most common receptor subtype in the brain, is implicated in vasoconstriction. Thus, systemic treatment with V1a receptor antagonists would be implicated in hypotonia. This implies that novel treatment concepts are needed to target AVP receptors not only at brain level but also in distinct brain areas, to offer alternative treatments for PTSD.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Humans; Rats; Rats, Brattleboro; Receptors, Vasopressin; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

Using the experimental model of post-traumatic stress disorder (stress-restress paradigm), we studied the dynamics of activity of the hypothalamic-pituitary-adrenal system (HPAS) in adult male rats, whose mothers were daily subjected to restraint stress on days 15-19 of pregnancy. Prenatally stressed males that were subjected to combined stress and subsequent restress exhibited not only increased sensitivity of HPAS to negative feedback signals (manifested under restress conditions), but also enhanced stress system reactivity. These changes persisted to the 30th day after restress. Under basal conditions, the number of cells in the hypothalamic paraventricular nucleus of these animals expressing corticotropin-releasing hormone and vasopressin was shown to decrease progressively on days 1-30. By contrast, combined stress and restress in control animals were followed by an increase in the count of CRH-immunopositive cells in the magnocellular and parvocellular parts of the paraventricular nucleus and number of vasopressin-immunopositive cells in the magnocellular part of the nucleus (to the 10th day after restress). Our results indicate a peculiar level of functional activity of HPAS in prenatally stressed males in the stress-restress paradigm: decreased activity under basal conditions and enhanced reactivity during stress.

Topics: Animals; Corticosterone; Corticotropin-Releasing Hormone; Disease Models, Animal; Female; Hypothalamo-Hypophyseal System; Male; Paraventricular Hypothalamic Nucleus; Pituitary-Adrenal System; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

Post-traumatic stress disorder (PTSD) is characterised by symptoms associated with maladaptive fear and stress responses, as well as with social detachment. The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) have been associated with both regulating fear and neuroendocrine stress responsiveness and social behaviour. However, there is only limited evidence for dysregulated peripheral OT and AVP levels in PTSD patients. The present study aimed to investigate basal salivary OT and AVP levels in trauma-exposed male and female police officers with and without PTSD. Saliva samples were collected during rest and OT and AVP levels were determined using a radioimmunoassay. Men and women were analysed separately, having adjusted for differences in trauma history, and for hormonal contraception use in women. The results showed that male PTSD patients had lower basal salivary OT levels, and did not differ in AVP levels compared to male trauma-exposed healthy controls after adjusting for childhood emotional abuse. There were no significant differences in basal salivary OT and AVP levels in women. Our findings indicate potential dysfunctioning of the OT system in male PTSD patients. Future studies are needed to replicate these findings and to further unravel the relationship between the OT and AVP systems, sex, trauma history and PTSD.

Topics: Adult; Case-Control Studies; Female; Humans; Male; Middle Aged; Oxytocin; Police; Saliva; Stress Disorders, Post-Traumatic; Vasopressins

The neuroendocrine mechanisms underlying anxiety-like state development in cycling female rats with different plasma estradiol levels have been studied in a stress-restress paradigm, an animal model of posttraumatic stress disorder (PTSD). The effect of stress-restress on the hypothalamic expression of corticotropin-releasing hormone (CRH) and vasopressin was analyzed by quantitative immunocytochemistry. Stress-restress was found to increase CRH expression in the hypothalamic paraventricular nucleus (PVN) on the 10th post-restress day, but the level of CRH expression in the PVN restored to the basal values on the 30th post-restress day in all experimental groups. It was shown an increase in vasopressin immunoreactivity in the PVN from the 10th to the 30th post-restress days in female rats exposed to stress during the estrus phase (low plasma estradiol level). In summary, female rats with low plasma estradiol level exhibited the most significant changes in the hypothalamic neuroendocrine system following stress-restress exposure. It might be hypothesized that hyperactivity of the hypothalamic circuit of the central vasopressinergic system is one of the possible mechanisms underlying PTSD-like state development in female rats in a stress-restress paradigm.

Topics: Animals; Corticotropin-Releasing Hormone; Disease Models, Animal; Estrous Cycle; Female; Gene Expression Regulation; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

The effects of immobilization stress from 15th to 19th days of gestation on hypothalamic-pituitary-adrenal (HPA) axis activity in the model of posttraumatic stress disorder (stress-restress paradigm) in adult female offspring were studied. The results showed that prenatal stressed female rats demonstrated enhanced stress reactivity and hypersensitive glucocorticoid feedback of HPA in response to the restress procedure. Moreover, decrease in basal level of corticosterone was detected only in prenatal stressed female rats. Immunocytochemical staining revealed that the effects of stress-restress procedure in control female rats were accompanied by the rise in corticotropin-releasing hormone immunoreactivity in the hypothalamic paraventricular nucleus, although over-expression of hypothalamic vasopressin was founded only in prenatal stressed rats. These data suggest that hypothalamic vasopressin was involved predominantly in posttraumatic stress disorder-like state in prenatal stressed female rats.

Topics: Animals; Corticosterone; Corticotropin-Releasing Hormone; Disease Models, Animal; Female; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Pregnancy; Rats; Stress Disorders, Post-Traumatic; Vasopressins

The present study was designed to reveal possible common and specific neuroendocrine mechanisms of depression and anxiety-like states in rodents. Animal models of depression and anxiety (in particular, posttraumatic stress disorder, PTSD) were applied including the learned helplessness and the stress-restress paradigms, respectively. Immunocytochemical staining revealed that depressive- and anxiety-like states in animals were accompanied by the rise in corticotropin-releasing hormone (CRH) immunoreactivity in the parvocellular division of the hypothalamic paraventricular nucleus (PVN). Decrease in vasopressin-immunoreactivity in early period of depressive-like state development was followed by the normalization of vasopressin content in the hypothalamic PVN in delayed period. Increased CRH and vasopressin immunoreactivity in the magnocellular part of the PVN in delayed period of anxiety-like state development was detected only in the stress-restress paradigm. These results suggest that CRH hyperdrive in the parvocellular PVN appears to be a common neuroendocrine abnormality for depressive- and anxiety-like states in animals, while over-expression of CRH and vasopressin in the magnocellular PVN represents a specific feature of anxiety/PTSD-like state.

Topics: Animals; Anxiety Disorders; Corticotropin-Releasing Hormone; Depressive Disorder; Disease Models, Animal; Helplessness, Learned; Immunohistochemistry; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Restraint, Physical; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

We report studies of the neuroendocrine mechanisms of development of an anxiety state in rats using the "stress-restress" experimental model of post-traumatic stress disorder. Immunocytochemical methods demonstrated significant increases in corticoliberin expression in both the parvo- and magnocellular parts of the paraventricular nucleus persisting to 10 days after presentation of the animals with repeated stress. Decreases in vasopressin expression were seen in the paraventricular nucleus of the animals on the first day after repeated stress. Vasopressin contents in the parvocellular part of the nucleus in animals of the experimental group were no different at 10 days from those in animals of the control group, while levels in the magnocellular part were increased. These data provide evidence for the involvement of the hypothalamic component of the vasopressinergic system (along with the corticoliberinergic system) in the pathogenetic mechanisms of the analog of post-traumatic stress disorder generated in this model.

Topics: Animals; Anxiety; Corticotropin-Releasing Hormone; Disease Models, Animal; Immunohistochemistry; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Stress Disorders, Post-Traumatic; Time Factors; Vasopressins

Many psychiatric disorders are a result of a disturbance in or exhaustion of the human stress response system. It is striking that many of these disorders such as depression, anxiety disorders and post-traumatic stress and somatoform and dissociative disorders are more prevalent in women. There are various explanations for this differing prevalence: it can be attributed to molecular, genetic, neurophysiological, relational and neurohormonal differences. Among the topics discussed are differences in exposure to chronic and traumatic stressors, the role of vasopressin and oxytocin in recovery and neurophysiological differences, the differentiating effect of hormones and neuropeptides such as oxytocin and vasopressin, the tend and befriend response and factors such as abuse and attachment disruption in early childhood.

Topics: Anxiety Disorders; Chronic Disease; Depressive Disorder; Dissociative Disorders; Female; Genetic Predisposition to Disease; Humans; Male; Oxytocin; Prevalence; Sex Factors; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

Neuroendocrine mechanisms of development of anxiety-like state in rats in experimental model of human post-traumatic stress disorder (PTSD), referred to as stress-restress paradigm, have been studied. Immunocytochemistry has revealed significant increase of CRH expression in both parvo- and magnocellular subdivisions of paraventricular nuclei up to 10th post-stress day. Significant reduction of vasopressin expression in rats' hypothalamic paravntricular nuclei has been detected on the 1st post-stress day. Vasopressin immunoreactivity in hypothalamus of stressed animals was indistinguishable from that in control group on the 10th post-stress day only in parvocellular subdivision of the paraventricular nucleus, while it was increased in magnocellular subdivision of the nucleus in experimental group compared to controls. The results imply a plausible role of hypothalamic vasopressin along with CRH on the development of PTSD.

Topics: Animals; Corticotropin-Releasing Hormone; Disease Models, Animal; Gene Expression Regulation; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Stress Disorders, Post-Traumatic; Time Factors; Vasopressins

Possible role of extrahypothalamic corticotrophin-releasing hormone (CRH) and vasopressin-producing centers in post-stress depression development were studied. We used genetically selected strains: KHA (Koltushi High Avoidance) and KLA (Koltushi Low Avoidance) rats developing different types of depression in the "learned helplessness" paradigm: the model analogues of endogenous (KHA strain) and exogenous (KLA strain) depression. Interstrain differences of control and stress-induced CRH- and vasopressin-expression in hippocampus and neocortex in the course of depression development in KHA and KLA rats were revealed using immuno-histochemical studies. It has been shown that a significant increase of CRH- and vasopressin-immune reactivity in hippocampus and neocortex of KHA rats occurred on the 10th post-stress day. We detected also decreased CRH- and vasopressin-expression in dorsal hippocampus, and increased CRH-immune reactivity in neocortex of KLA rats in the same post-stress period. These findings imply that extrahypothalamic CRH- and vasopressin-ergic systems appear to be involved in pathogenesis mechanisms of model analogues of endogenous and exogenous depression in different ways.

Topics: Animals; Corticotropin-Releasing Hormone; Depression; Helplessness, Learned; Hippocampus; Male; Neocortex; Pituitary-Adrenal System; Rats; Rats, Inbred Strains; Species Specificity; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

Ohmefentanyl (OMF) is a new mu opioid receptor agonist with high affinity and selectivity, and possesses anesthetic activity. With radioimmunoassay, the plasma levels of cortisol (C), corticosterone (CS) and antidiuretic hormone (ADH) in rats were measured. The results indicated that no significant differences in the plasma C, CS and ADH levels were observed between the saline control group and the OMF-treated group. Trauma (bone-crush injury) increased significantly the plasma CS level. However, pretreatment with OMF 4.0 micrograms.kg-1 reduced markedly the CS plasma levels in trauma-treated rats. The results suggest that OMF anesthesia itself showed no obvious effect on the plasma concentration of C, CS and ADH, but blocked the hormoral stress responses such as the increment of plasma CS level caused by trauma stimulus.

Topics: Analgesics; Animals; Corticosterone; Fentanyl; Male; Rats; Stress Disorders, Post-Traumatic; Vasopressins