pica and Nausea

We review information about the potential mechanisms underlying nausea and vomiting in pregnancy (NVP), food cravings, and/or aversions in pregnancy. In addition to providing overviews about genetic predispositions and hormonal associations with appetite sensations and NVP, we review two functional explanations: the "maternal and embryo protection" and the "placental growth and development" hypotheses. We conclude with a discussion about the kinds of data that would enable us to better evaluate the relative advantages and disadvantages of NVP across disparate resource and ecological conditions.

Topics: Adaptation, Physiological; Appetite; Cultural Deprivation; Feeding and Eating Disorders; Female; Food Preferences; Humans; Maternal Nutritional Physiological Phenomena; Models, Biological; Nausea; Pica; Pregnancy; Pregnancy Complications; Vomiting

Women all over the globe report physical and appetite sensations in early pregnancy, and this study contributes to this growing literature by reporting on the appetite sensations experienced by pregnant women from rural Tanzania. Appetite changes associated with 545 pregnancies were compiled from surveys conducted to report on the prevalence of appetite loss, nausea, vomiting, dizziness, joint pain, cravings, aversions, and pica experienced by agropastoral women from rural north-central Tanzania. In addition to these symptoms, specific craved and aversive food groups are described. Statistical associations among appetite sensations, NVP, and birthweight are tested. The only symptom associated with a lower average birth weight for newborns was vomiting. In addition to investigating micronutrient content and chemical properties of specific food and non-food items, future research should include assessing relationships among various appetite sensations and short- and long-term health outcomes for both the mother and child.

Topics: Adult; Appetite; Birth Weight; Cross-Sectional Studies; Female; Food Preferences; Humans; Infant, Low Birth Weight; Infant, Newborn; Morning Sickness; Nausea; Pica; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prevalence; Rural Population; Tanzania; Vomiting

Nutrition assessment and counseling are integral components of preconception and prenatal care. The average-size woman should gain between 11.25 and 15.75 kg (25 and 35 lb) during a normal pregnancy. Some factors identify the pregnant woman with a nutrition risk. Vitamin and mineral supplementation should be based on a dietary assessment. Common discomforts of pregnancy frequently can be managed with dietary modification and safe pharmacotherapeutics. The coordinated efforts of health care providers, registered dietitians, the Women, Infants, and Children (WIC) nutrition program, local health departments and Cooperative Extension Service offices can provide appropriate nutrition assessment, education and intervention.

Topics: Caffeine; Constipation; Female; Humans; Lactose Intolerance; Nausea; Nutrition Assessment; Nutritional Physiological Phenomena; Pica; Pregnancy; Pregnancy Complications; Sodium, Dietary; Substance-Related Disorders; Vomiting; Weight Gain

Xiaobanxia Decoction (XBXD), a traditional antiemetic formula, is effective in preventing chemotherapy-induced nausea and vomiting (CINV), but its underlying mechanism has not been fully clarified.. To investigate whether the antiemetic mechanisms of XBXD against CINV is associated with the reduction of GSDME-mediated pyroptosis and the alleviation of gastrointestinal inflammation induced by cisplatin.. We established the in vivo pica rat model and the in vitro small intestinal epithelial cell (IEC-6 cell) injury model by cisplatin challenge. The levels of ROS, IL-1β, IL-18, HMGB1 were measured by ELISA. The histopathological changes of gastrointestinal (GI) tissues were examined by HE staining. The expression and localization of GSDME in GI tissues were determined by IHC. The GSDME mRNA expression in GI tissues was determined by RT-PCR. The IEC-6 cell viability was detected by CCK-8. The morphology of IEC-6 cells was observed by optical microscope and scanning electron microscopy. Pyroptosis was examined using Hoechst33342/PI staining. The intracellular ROS levels were measured with the fluorescent probe DCFH-DA. The expression levels of JNK, p-JNK, Bax, Bcl-2, caspase-9, caspase-3 and GSDME in GI tissues and IEC-6 cells were determined by WB.. We found that the cumulative kaolin intake (pica behavior, analogous to emesis) significantly increased in cisplatin-treated rats, accompanied by significant inflammatory pathological changes of GI tissues. XBXD decreased the cumulative kaolin intake and alleviated GI inflammation in cisplatin-treated rats by inhibiting the activation of the ROS/JNK/Bax signaling pathway and by reducing GSDME-mediated pyroptosis. Additionally, cisplatin damaged IEC-6 cells by activating GSDME-dependent pyroptosis. XBXD reduced GSDME-mediated IEC-6 cell pyroptotic death by regulating the ROS/JNK/Bax signaling pathway.. This study suggested that GSDME-mediated pyroptosis greatly contributes to the occurrence of CINV, and suppressing GSDME-mediated pyroptosis is the important antiemetic mechanism of XBXD.

Topics: Animals; Antiemetics; Antineoplastic Agents; bcl-2-Associated X Protein; Caspase 3; Cisplatin; Inflammation; Kaolin; Nausea; Pica; Pyroptosis; Rats; Reactive Oxygen Species; Vomiting

Pica refers to eating nonfood substances. The pica behavior has been the focus of attention in physiological and pharmacological studies, because its consumption is a good marker of nausea in laboratory rats, which cannot vomit due to neuroanatomical reasons. Almost all pica studies with rats have used kaolin clay pellets as nonfood substances. The present study primarily aimed to explore an alternative (or more suitable) substance to kaolin for detection of nausea induced by emetic drugs. Two calcium compounds, gypsum and lime, were evaluated in this study. An injection of lithium chloride (LiCl) increased pica behavior not only in the rats given kaolin but also in the rats given gypsum, suggesting that gypsum consumption could be used as an indicator of nausea. However, its sensitivity was no greater than that of kaolin consumption. In addition, lime is not a useful marker for nausea because the size of pica was small in the LiCl-injected rats, and did not differ from the control in the cisplatin-injected rats. In short, the superiority of kaolin as a test substance for nausea could not be overturned. However, the fact that nauseous rats displayed pica behavior with gypsum and lime refutes the claim that aluminosilicate, the main component of kaolin, is the critical determinant of emetic-caused pica in laboratory rats.

Topics: Animals; Antineoplastic Agents; Calcium Compounds; Calcium Sulfate; Cisplatin; Emetics; Kaolin; Lithium Chloride; Nausea; Pica; Rats

Nausea and vomiting are common gastrointestinal side effects of oxaliplatin chemotherapy used for the treatment of colorectal cancer. However, the mechanism underlying oxaliplatin-induced nausea and vomiting is unknown. The stomach is involved in the emetic reflex but no study investigated the effects of oxaliplatin treatment on the stomach. In this study, the in vivo effects of oxaliplatin treatment on eating behaviour, stomach content, intrinsic gastric neuronal population, extrinsic innervation to the stomach, levels of mucosal serotonin (5-hydroxytryptamine, 5-HT), and parasympathetic vagal efferent nerve activity were analysed. Chronic systemic oxaliplatin treatment in mice resulted in pica, indicated by increased kaolin consumption and a reduction in body weight. Oxaliplatin treatment significantly increased the stomach weight and content. The total number of myenteric and nitric oxide synthase-immunoreactive neurons as well as the density of sympathetic, parasympathetic, and sensory fibres in the stomach were decreased significantly with oxaliplatin treatment. Oxaliplatin treatment significantly increased the levels in mucosal 5-HT and the number of enterochromaffin-like cells. Chronic oxaliplatin treatment also caused a significant increase in the vagal efferent nerve activity. The findings of this study indicate that oxaliplatin exposure has adverse effects on multiple components of gastric innervation, which could be responsible for pica and gastric dysmotility.

Topics: Animals; Mice; Nausea; Oxaliplatin; Pica; Serotonin; Stomach; Vomiting

Donepezil, an acetylcholinesterase inhibitor, is associated with gastrointestinal symptoms, such as nausea, vomiting, and anorexia, which may affect adherence to continuous therapy. Since Rikkunshi-To, a Japanese herbal medicine, activates the ghrelin signaling pathway and promotes gastrointestinal function, it is administered to prevent gastrointestinal symptoms. We herein investigated whether donepezil-induced gastrointestinal side effects in mice are ameliorated by Rikkunshi-To and if its therapeutic efficacy is mediated by ghrelin. Since pica behavior, the ingestion of kaolin, correlates with nausea and vomiting in humans, donepezil was intraperitoneally administered with or without Rikkunshi-To daily to mice, and food and kaolin intakes were monitored. The effects of donepezil on intestinal motility and a ghrelin receptor antagonist on donepezil-induced pica behavior, anorexia, and changes in intestinal motility were examined in mice treated with Rikkunshi-To. Pica behavior and anorexia were significantly induced by donepezil and significantly inhibited by Rikkunshi-To. Intestinal motility was significantly suppressed by donepezil and promoted by Rikkunshi-To. Furthermore, the therapeutic effects of Rikkunshi-To were antagonized by the ghrelin receptor antagonist. The present results support the therapeutic efficacy of Rikkunshi-To against donepezil-induced gastrointestinal side effects.

Topics: Acetylcholinesterase; Animals; Anorexia; Donepezil; Drugs, Chinese Herbal; Ghrelin; Humans; Kaolin; Medicine, Kampo; Mice; Nausea; Pica; Receptors, Ghrelin; Vomiting

Studies show that traditional Chinese medicine (TCM), such as Liujunanwei (LJAW) decoction, can play important roles in alleviating side effects of chemotherapy. The purpose of this study was to understand how LJAW can counter chemotherapy-induced emesis

Topics: Animals; Antineoplastic Agents; Cisplatin; Kaolin; Nausea; Pica; Rats; RNA, Ribosomal, 16S; Vomiting

During pregnancy, women tend to improve their lifestyle habits and refine their dietary intake. Quite often, however, these dietary improvements take an unhealthy turn, with orthorexia nervosa (ON) practices being apparent. The aim of the present pilot cross-sectional study was to assess the prevalence of ON tendencies and the incidence of pica and record diet practices in a sample of pregnant women. A total of 157 pregnant women were recruited through private practice gynecologists during the first months of 2021. Nutrition-related practices were recorded, orthorexic tendencies were assessed using the translated and culturally adapted Greek version of the ORTO-15 questionnaire, pica practices were evaluated with a binary question and nausea and emesis during pregnancy (NVP) was evaluated using the translated modified Pregnancy-Unique Quantification of Emesis and Nausea (mPUQE). Only two women reported pica tendencies, with ice and snow being the consumed items. The majority (61.1%) of women reported improving their diet since conception was achieved. Folic acid and iron oral nutrient supplements (ONS) were reportedly consumed by the majority of participants (87.9% and 72.6%, respectively) and 9.6% reported using herbal medicine products. The ORTO-15 score was reduced with tertiary education attainment, ART conception, being in the third trimester of pregnancy, consumption of folic acid and MV supplements and was only increased among women who were at their first pregnancy. The majority of participants experienced severe NVP and the remaining experienced moderate NVP. NVP was associated with lower hemoglobin levels, lack of supplementary iron intake, avoidance of gluten-containing foods, as well as with increased gestational weight gain. The results highlight the need to screen pregnant women for disturbed eating behaviors and nutrition-related problems, in order to ensure a healthy pregnancy outcome.

Topics: Cross-Sectional Studies; Female; Folic Acid; Humans; Iron; Morning Sickness; Nausea; Pica; Pilot Projects; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Vomiting

Niacin deficiency causes pellagra, the symptoms of which include dermatitis, diarrhoea and dementia. Investigating the mechanism underlying these phenotypes has been challenging due to the lack of an appropriate animal model. Here, we report a mouse model of pellagra-related nausea induced by feeding mice a low-niacin diet and administering isoniazid (INH), which is thought to induce pellagra. Mice fed a normal or low-niacin diet received INH (0·3 or 1·0 mg/mg per animal, twice daily, 5 d), and nausea was evaluated based on pica behaviour, which considered the rodent equivalent of the emetic reflex. Furthermore, the effect of therapeutic niacin administration on nausea was evaluated in this model. Urinary and hepatic metabolite levels were analysed by LC coupled with MS. INH-induced pica was observed in mice fed a low-niacin diet but not in those fed a normal diet. Levels of urinary metabolites, such as 1-methyl-2-pyridone-5-carboxamide, kynurenic acid and xanthurenic acid, were significantly reduced in the mice treated with INH compared with those that did not receive INH. Furthermore, niacin supplementation prevented pica and restored the levels of some metabolites in this mouse model. Our findings suggest that INH-related nausea is pellagra-like. We also believe that our newly established method for quantifying pica is a useful tool for investigating the mechanisms of pellagra-related nausea.

Topics: Animals; Dietary Supplements; Disease Models, Animal; Isoniazid; Mice; Nausea; Niacin; Pellagra; Pica

Topics: Administration, Oral; Animals; Bone Density Conservation Agents; Drugs, Chinese Herbal; Female; Gastrointestinal Motility; Ghrelin; Injections, Subcutaneous; Nausea; Ovariectomy; Phytotherapy; Pica; Rats, Wistar; Signal Transduction; Teriparatide

The cytotoxic drugs used in chemotherapy are often accompanied by nausea and vomiting. Despite the use of antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) remain significant side effects for cancer patients and are associated with serotonin type 3 receptor (5-HT

Topics: Animals; Antiemetics; Antineoplastic Agents; Appetite; Cisplatin; Farnesol; Male; Nausea; Oils, Volatile; Pica; Rats; Rats, Wistar; Receptors, Serotonin, 5-HT3; Sesquiterpenes; Vomiting; Weight Loss

Topics: Adult; Female; Humans; Nausea; Pain; Pica; Soaps; Vomiting

Nausea and diarrhea are common yet inconsistent side effects of abdominal and pelvic irradiation. Their frequency, chronicity, and severity vary greatly, and the reasons for inter-subject variability are unknown. We studied the potential for radiation-induced changes in amino acid absorption and mucosal barrier function to lead to gastrointestinal toxicity. We found profound and prolonged changes in the absorption and secretion of several electrolytes and nutrients, caused by changes in transporter function, after radiation doses as low as 1 to 3 Gy. After identifying absorbed and non-absorbed amino acids, we demonstrated the role of a beneficial amino acid drink to alleviate radiation-related gastrointestinal symptoms in a mouse model.

Topics: Amino Acids; Animals; Disease Models, Animal; Electrolytes; Fluid Therapy; Gastrointestinal Absorption; Gastrointestinal Diseases; Glucose; Male; Mice; Nausea; Pica; Radiation Injuries; Rehydration Solutions

While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (<24 h) phase following treatment, the anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments.

Topics: Animals; Anorexia; Body Weight; Cisplatin; Glucagon-Like Peptide-1 Receptor; Infusions, Intraventricular; Male; Nausea; Neurons; Peptide Fragments; Pica; Proglucagon; Rats; Rhombencephalon; Solitary Nucleus

Three experiments were conducted showing rats' pica behavior (kaolin clay intake) due to running in activity wheels. The amount of kaolin consumed was a positive function of the available time of voluntary running (20, 40, or 60 min), although this relationship was blunted by a descending (i.e., 60 → 40 → 20 min) test series of execution (Experiment 1). Pica was also generated by forced running in a motorized wheel for 60 min as a positive function of the speed of wheel rotations at 98, 185, or 365 m/h, independent of the order of execution (Experiment 2). Voluntary running generated more pica than did forced running at 80 m/h, although the distance travelled in the former condition was 27% lesser than that in the latter condition (Experiment 3). Because kaolin intake is regarded as a reliable measure of nausea in rats, these results show that wheel running, either voluntary or forced, induces nausea in rats.

Topics: Aluminum Silicates; Animals; Behavior, Animal; Clay; Disease Models, Animal; Energy Intake; Feeding Behavior; Kaolin; Male; Motor Activity; Nausea; Physical Exertion; Pica; Rats, Wistar; Reproducibility of Results; Time Factors

We have recently demonstrated that voluntary or forced running in activity wheels yields pica behavior (kaolin clay intake) in rats (Nakajima, 2016; Nakajima and Katayama, 2014). The present study provides experimental evidence that a single 40-min session of swimming in water also generates pica in rats, while showering rats with water does not produce such behavior. Because kaolin intake has been regarded as a measure of nausea in rats, this finding suggests that swimming activity, as well as voluntary or forced running, induces nausea in rats.

Topics: Animals; Eating; Kaolin; Male; Nausea; Pica; Rats; Swimming

We investigated the effects of olanzapine on cisplatin-induced pica (the consumption of non-nutrient materials such as kaolin) and glucose homeostasis in rats to clarify the effects of olanzapine when used as an anti-emetic drug. Rats were injected intraperitoneally (i.p.) with either 5 mg/kg cisplatin or saline. Additionally, 2 or 10 mg/kg olanzapine were administered i.p. to the rats 10 min before the administration of cisplatin and subsequently administered every 24 h for 3 d. Kaolin and food intake was measured using an automatic monitoring apparatus. Plasma glucose levels were measured by an enzyme electrode method. The plasma levels of insulin and intact proinsulin were measured by enzyme-linked immunosorbent assay (ELISA). The proinsulin-to-insulin (P/I) ratio was calculated. Cisplatin significantly increased kaolin intake, but decreased food intake and body weight up to 72 h. Olanzapine had no effect on these parameters. Neither olanzapine nor cisplatin alone had a significant effect on the plasma levels of glucose, insulin, or proinsulin. However, a combination of olanzapine and cisplatin significantly decreased plasma insulin levels, but increased plasma intact proinsulin levels and the P/I ratio. Our results suggest that an additive deterioration of insulin-secreting beta-cell function and disturbance of glucose homeostasis should be considered during treatment of patients with olanzapine for cisplatin-induced nausea and vomiting.

Topics: Animals; Antiemetics; Antineoplastic Agents; Benzodiazepines; Blood Glucose; Cisplatin; Eating; Homeostasis; Kaolin; Male; Nausea; Olanzapine; Pica; Proinsulin; Rats, Wistar; Vomiting

Intermittent subcutaneous injection of teriparatide, an active fragment of human parathyroid hormone, is clinically used for the treatment of osteoporosis. Patients suffer from nausea, which is one of the side effects teriparatide induces; however, the etiology of teriparatide-induced nausea remains unknown. We have reported pica, kaolin ingestion behavior, can be used as an assessment of nausea-related response in rats. In this study, we investigated the characteristics of teriparatide-induced pica and the abilities of anti-emetic drugs to inhibit teriparatide-induced pica. Male and female adolescent (4-week-old), young (8-week-old), and adult (30-week-old) naive rats, and ovariectomized (OVX: 17-week-old) and sham-operated (17-week-old) rats subcutaneously received teriparatide (0.4 mg/kg, n=4), and their kaolin and food intakes were monitored for 24 h after the injection. Among the tested rats, we found that OVX rats, rather than male, female, and sham-operated rats, showed marked teriparatide-induced pica (0 mg/kg: 0.17±0.07 g, 0.4 mg/kg: 6.18±0.91 g). Teriparatide-induced pica in OVX rats was inhibited by intraperitoneal pretreatment with serotonin 5-HT3 (granisetron 0.5 mg/kg), dopamine D2 (prochlorperazine 0.5 mg/kg), neurokinin NK1 (fosaprepitant 1 mg/kg), and histamine H1 (diphenhydramine 10 mg/kg) receptor antagonists to 70%, 11%, 19%, and 59% of that in vehicle-treated control, respectively. These results suggest that teriparatide-induced pica in OVX rats has the potential to reflect teriparatide-induced nausea; 5-HT3, D2, NK1, and H1 receptor activation is involved in the development of this behavior; antagonists of these receptors have the potential to be medical candidates used as treatments for teriparatide-induced nausea in human patients.

Topics: Age Factors; Animals; Anorexia; Antiemetics; Diphenhydramine; Disease Models, Animal; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Female; Granisetron; Histamine H1 Antagonists; Kaolin; Male; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Neurotransmitter Agents; Ovariectomy; Pica; Prochlorperazine; Rats, Wistar; Serotonin 5-HT3 Receptor Antagonists; Teriparatide

Although substance P (SP) and neurokinin NK1 receptors have been reported to be involved in cisplatin-induced acute and delayed emesis, their precise roles remain unclear. Pica, the consumption of non-nutrient materials such as kaolin in rats, can be used as a model of nausea in humans. We investigated the time-dependent changes in cisplatin-induced pica and the involvement of SP and NK1 receptors in this behaviour.. Rats were administered cisplatin with or without a daily injection of a 5-HT3 receptor antagonist (granisetron) or an NK1 receptor antagonist (aprepitant), and kaolin intake was then monitored for 5 days. The effects of granisetron on the cisplatin-induced expression of preprotachykinin-A (PPT-A) mRNA, which encodes mainly for SP, and on SP release in the medulla, measured by in vivo brain microdialysis, were also investigated.. Cisplatin induced pica within 8 h of its administration that continued for 5 days. Granisetron inhibited the acute phase (day 1), but not the delayed phase (days 2-5), of pica, whereas aprepitant abolished both phases. Within 24 h of the injection of cisplatin, PPT-A mRNA expression and SP release in the medulla were significantly increased; these findings lasted during the observation period and were inhibited by granisetron for up to 24 h.. The profiles of cisplatin-induced pica in rats are similar to clinical findings for cisplatin-induced emesis in humans, and we showed that SP production in the medulla and activation of NK1 receptors are involved in this cisplatin-induced pica.

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Eating; Granisetron; Kaolin; Male; Medulla Oblongata; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Pica; Protein Precursors; Rats, Wistar; Receptors, Neurokinin-1; Receptors, Serotonin, 5-HT3; RNA, Messenger; Serotonin Antagonists; Solitary Nucleus; Substance P; Tachykinins

Voluntary running in an activity wheel establishes aversion to paired taste in rats. A proposed mechanism underlying this taste aversion learning is gastrointestinal discomfort caused by running. We tested this hypothesis by measuring the pica behavior (kaolin clay intake) of rats, because it is known that rats engage in pica behavior after various nausea-inducing treatments including irradiation, motion sickness, and injection of emetic drugs such as lithium chloride (LiCl). Following a demonstration of the already-known phenomenon of LiCl-based pica in Experiment 1, we successfully showed running-based pica behavior in Experiment 2 where the running treatment was compared with a non-running control treatment (i.e., confinement in a locked wheel). These results suggest that not only LiCl but also running induces nausea in rats, supporting the gastrointestinal discomfort hypothesis of running-based taste aversion learning.

Topics: Abdominal Pain; Aluminum Silicates; Animals; Avoidance Learning; Behavior, Animal; Clay; Disease Models, Animal; Dysgeusia; Emetics; Injections, Intraperitoneal; Kaolin; Lithium Chloride; Male; Models, Biological; Motor Activity; Nausea; Physical Exertion; Pica; Rats, Wistar; Stress, Physiological

Oxycodone, a semisynthetic opioid analgesic, is frequently prescribed for the management of pain. Side effects of nausea and emesis affect patient compliance and limit its therapeutic use. The present study established that an antinociceptive dose of oxycodone (15 mg/kg; oral) induces the pica response. We found sex differences in the temporal course of pica, with females having a longer duration. Opioid receptors mediated the pica response, as 1.0 mg/kg naloxone transiently attenuated and 2.0 mg/kg naloxone blocked pica. A κ-selective antagonist failed to block the response, suggesting mediation by μ opioid receptor. For further validation, we used the well established kaolin intake model to assess pica with the chemotherapeutic drug cisplatin as a positive control. Oxycodone and cisplatin significantly increased kaolin intake 4- to 7-fold, and the wet weight of stomach was elevated 2- to 3-fold. To examine the underlying neural circuitry, we investigated c-fos activation in the area postrema and nucleus of solitary tract (NTS). Oxycodone treatment significantly increased the number of c-fos-positive neurons in the area postrema and NTS compared with water controls. As expected, cisplatin also increased the number of c-fos-positive cells in these regions. In the area postrema, the oxycodone effect was greater than cisplatin, especially at 2 h. These results indicate that an antinociceptive dose of oxycodone is associated with the expression of pica, a pro-emetic response.

Topics: Analgesics, Opioid; Animals; Antiemetics; Antineoplastic Agents; Brain; Cisplatin; Drug Evaluation, Preclinical; Emetics; Female; Humans; Kaolin; Male; Narcotic Antagonists; Nausea; Oxycodone; Pica; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Receptors, Opioid, mu; Sex Characteristics; Time Factors; Vomiting

Cancer chemotherapy drugs, such as cisplatin, are extremely potent for producing nausea and vomiting. The acute effects of these treatments are partly controlled using anti-emetic drugs, but the delayed effects (>24 h), especially nausea, are much more difficult to treat. Furthermore, cisplatin induces a long-term (up to 48 h) increase in pica in rats. Pica is manifested as an increase in consumption of kaolin (clay) and is used as a measure of visceral sickness. It is unknown what brain pathways might be responsible for this sickness associated behavior. As a first attempt to define this neural system, rats were injected (i.p.) with 3, 6, or 10 mg/kg cisplatin (doses reported to produce pica) and sacrificed at 6, 24, or 48 h to determine brain Fos expression. The primary results indicate: 1) increasing the dose of cisplatin increased the magnitude and duration of brain Fos expression, 2) most excitatory effects on hindbrain nucleus of the solitary tract (NTS) and area postrema (AP) Fos expression occurred within 24 h after cisplatin injection, 3) 6 and 10 mg/kg cisplatin treatment produced large increases in Fos expression in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST), including 48 h after injection, and 4) cisplatin treatment produced little effect on Fos expression in the paraventricular and supraoptic nuclei of the hypothalamus. These results indicate that cisplatin activates a neural system that includes the dorsal vagal complex (NTS and AP), CeA, and BNST.

Topics: Animals; Antineoplastic Agents; Brain; Cisplatin; Dose-Response Relationship, Drug; Immunohistochemistry; Male; Nausea; Neural Pathways; Pica; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Vomiting

This study aimed to dissect the mechanisms involved in malaise induced by the anti-cancer drug cisplatin by attempting to uncouple its effects on locomotor activity, arguably at least partly indicative of fatigue, from those effects indicative of emesis (pica, gastric stasis, reduced food intake) using pharmacological agents in the rat. Over 2 days cisplatin (6 mg/kg i.p.) reduced food intake, stimulated kaolin consumption, increased the wet weight of gastric contents and reduced locomotor activity. In animals treated with cisplatin: the 5-HT3 receptor antagonist ondansetron (1 mg/kg s.c. bd.) had no effect on either activity or weight of gastric contents but did increase food intake on day 1 (P<0.05) and the total over both days (27.6+/-1.8 vs. 19.9+/-2.3g, P<0.05), reducing kaolin consumption on day 2 (P<0.01) but not the total over both days; the NK1 receptor antagonist GR205171 (1 mg/kg s.c. bd.) was without effect on activity, but reduced the wet weight of gastric contents (P<0.05), increased food intake on day 2 (P<0.01) and total consumption over both days (28.1+/-1.7 g vs. 19.9+/-2.3 g; P<0.05) and reduced kaolin consumption on day 2 (P<0.05) but not over both days; dexamethasone (2 mg/kg s.c. bd.) blocked the cisplatin-induced reduction in activity on days 1 and 2 (P<0.01), reduced the wet weight of gastric contents by 43% (P<0.01), reduced kaolin consumption on both days (P<0.01) and arguably decreased the reduction in food intake caused by cisplatin. This study has revealed novel insights into the different spectra of activities of 5-HT3 and NK1 receptor antagonists and dexamethasone, which have implications for therapeutic strategies to alleviate the emetic, anorectic, dyspeptic and activity-reducing effects of anti-cancer chemotherapy.

Topics: Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Dexamethasone; Eating; Gastric Emptying; Male; Motor Activity; Nausea; Neurokinin-1 Receptor Antagonists; Ondansetron; Pica; Piperidines; Rats; Rats, Wistar; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Tetrazoles

Ritonavir, a protease inhibitor drug, is commonly used in AIDS therapy. As with other chemotherapeutic drugs that cause gastrointestinal adverse effects, ritonavir treatment is associated with significant nausea and vomiting. This study investigated whether Scutellaria baicalensis, and its active flavonoid constituent, baicalein, attenuate the gastrointestinal effects of ritonavir. The effects of herb administration were evaluated in ritonavir-treated rats using a rat pica model, which simulates nausea and vomiting in humans. The effects of herb administration on gastric emptying in rats were also measured. Ritonavir treatment resulted in increased kaolin intake or severe pica, the intensity of which was reduced significantly with S. baicalensis administration (1 mg kg(-1); P<0.05). High-performance liquid chromatography analysis of S. baicalensis showed the presence of an extremely potent flavonoid constituent, baicalein. The study aimed to determine if baicalein contributed to the anti-pica effect of the extract. It was observed that baicalein dose-dependently decreased pica in ritonavir-treated rats (P<0.001). In addition to inducing pica, ritonavir also significantly delayed gastric emptying, which could contribute to ritonavir-induced gastrointestinal dysfunction. When S. baicalensis extract was administered to ritonavir-treated rats the delayed gastric emptying was significantly attenuated (P<0.05). The results suggest that S. baicalensis and the constituent baicalein reduce the gastrointestinal dysfunction caused by ritonavir. It is concluded that S. baicalensis may potentially have a role to play in reducing drug-induced adverse effects.

Topics: Animals; Antiemetics; Antioxidants; Disease Models, Animal; Dose-Response Relationship, Drug; Flavanones; Flavonoids; Gastric Emptying; HIV Protease Inhibitors; Kaolin; Male; Nausea; Pica; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Ritonavir; Scutellaria baicalensis; Vomiting

Rats lack the emetic reflex but exhibit pica in response to stimuli that induce emesis in species with an emetic reflex, hence it has been proposed that pica may be analogous to emesis in species lacking the reflex. In the present study, we investigated whether pica was present in Suncus murinus (with an emetic reflex) as well as in rats and mice (without emetic reflex) to provide a further insight to the validity of pica as a model for nausea/vomiting. Cisplatin (6 mg/kg, i.p.) induced pica in rats, indicated by a significant increase in kaolin consumption at 24 h (but not 48 h) post-treatment whereas we failed to demonstrate this effect in mice (inbred or outbred strain, 6 or 20 mg/kg i.p.) and whilst cisplatin (20 mg/kg, i.p.) induced emesis in Suncus, kaolin intake was not significantly affected. Furthermore, cisplatin significantly increased the weight of gastric contents at 48 h post-injection in rats and mice indicating delayed gastric emptying whereas this effect was not present in Suncus. These results show that Suncus and two strains of mice, unlike rats, do not develop pica in response to cisplatin which suggests that the consumption of kaolin induced by cisplatin may not be associated with whether or not an emetic reflex is present. The differences in ingestive behaviour and gastric response between species with and without an emetic reflex in response to cisplatin treatment as well as the difference between mice and rats, is discussed in relation to the selection of models for the study of nausea and vomiting.

Topics: Animals; Body Weight; Cisplatin; Disease Models, Animal; Drinking; Eating; Kaolin; Male; Mice; Nausea; Organ Size; Pica; Rats; Shrews; Species Specificity; Stomach; Time Factors

Grape-seed (Vitis spp.) extract (GSE) is a widely used antioxidant dietary supplement. Chemotherapeutic agents such as cisplatin induce oxidative damage in the gastrointestinal tract and cause nausea and vomiting.. A rat model of simulated emesis was used to observe that cisplatin significantly increased kaolin consumption (or pica). Three GSEs from different sources were used in this study.. High-performance liquid chromatographic analysis of five major constituents (gallic acid, catechin, epicatechi, procyanidin B2, and epicatechin gallate) revealed that each constituent had different levels in the three GSEs. Extract #1, prepared in the laboratory of the investigators, had the lowest total polyphenol content (27.27 mg/g); Extract #2, obtained from a dietary supplement company in the United States, had a somewhat higher level (35.84 mg/g); and Extract #3, obtained from China, had the highest level (194.21 mg/g). Subsequently these GSEs were intraperitoneally administered in rats to evaluate their ability to decreasing cisplatin induced pica. At 10 mg/kg all three GSEs, with varying degrees of effect, decreased cisplatin-induced pica. The areas under the curves of kaolin intake from time 0 to 72 hours, compared to those in the cisplantin-only group, were reduced 45% for Extract #1 (p < 0.01), 54% for Extract #2 (p < 0.01), and 66% Extract #3 (p < 0.001).. The study data showed variable polyphenol contents and proportions in the three GSEs correlated to variable pharmacologic effects, indicating the importance of standardization of herbal product preparations. However further increasing of the GSE doses reversed the antipica effects of GSEs, probably because of their pro-oxidant effects. Results from this study suggest that an appropriate dose of GSE has therapeutic value in treating cisplatin-induced emesis.

Topics: Animals; Antiemetics; Antioxidants; Area Under Curve; Cisplatin; Disease Models, Animal; Dose-Response Relationship, Drug; Flavonoids; Male; Nausea; Phenols; Phytotherapy; Pica; Plant Extracts; Polyphenols; Rats; Rats, Wistar; Seeds; Vitis; Vomiting

Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting.

Topics: Animals; Antineoplastic Agents; Antioxidants; Cisplatin; Disease Models, Animal; Free Radical Scavengers; Male; Nausea; Panax; Phytotherapy; Pica; Plant Extracts; Rats; Rats, Wistar; Scutellaria; Vomiting

Nausea/vomiting are significant side effects associated with the use of chemotherapy in cancer patients. Treatment of nausea/vomiting caused by cisplatin, a potent chemotherapeutic agent and one of the most emetogenic stimuli, requires a combination of different antiemetic drugs. In this study, we investigated the effects of Scutellaria baicalensis, an antioxidant herbal medicine, on cisplatin-induced nausea using a rat model.. Rats react to emetic/nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by pica or increased consumption of kaolin (a type of clay). We measured pica in rats to quantify cisplatin-induced nausea, and to evaluate the antinausea effect of pretreatment with S. baicalensis extract (SbE) given intraperitoneally.. Cisplatin at 3 mg/kg induced significant pica accompanied by reduced food intake, suggesting the presence of nausea. Hence, this cisplatin dose was selected for testing the antinausea activity of SbE. Cisplatin-induced pica decreased significantly when animals were pretreated with SbE at doses of 1 mg/kg and 3 mg/kg ( P<0.01). At a higher SbE dose (10 mg/kg), kaolin consumption increased, rather than further decreased, and was significantly different from that in the groups treated with low SbE doses.. SbE pretreatment decreased cisplatin-induced kaolin intake in the rat model of simulated nausea, suggesting that SbE and its active constituent(s) may play a therapeutic role in chemotherapy-induced emesis. Absence of therapeutic effect at the highest tested SbE dose could have been a result of prooxidant activity often associated with excess antioxidant concentration.

Topics: Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Injections, Intraperitoneal; Kaolin; Male; Nausea; Pica; Plant Roots; Rats; Rats, Wistar; Scutellaria baicalensis

In a direct test of conditioned antisickness (CAS; B. T. Lett, 1983) theory, the authors measured emesis in ferrets and found those with a history of forward pairings of pentobarbital and lithium to have fewer and shorter bouts of emesis on test, whether induced by lithium or, in a subsequent test, by the highly emetogenic anticancer drug cisplatin. In an indirect test of her CAS theory, B. T. Lett (1992) paired interoceptive (drug) or place cues with lithium chloride toxicosis and found that rats with a forward-pairings history ate less food than controls on a forward-pairing test, consistent with conditioned sickness rather than CAS. But rats eat dirt or clay in response to sickness and adaptively eat small amounts of food when clay is not available. We substituted clay (kaolin) for food in a partial procedural replication of B. T. Lett's (1992, Experiment 1) experiment and found that rats with a history of forward pairings of pentobarbital and lithium ate less kaolin, which is consistent with CAS.

Topics: Animals; Association Learning; Avoidance Learning; Conditioning, Classical; Emetics; Ferrets; Kaolin; Male; Nausea; Pica; Rats; Rats, Sprague-Dawley; Species Specificity; Taste; Vomiting

Frequency and severity of nausea and of vomiting during pregnancy, and of pronounced dietary cravings and aversions, were determined in a series of South African rural and urban black, Indian, coloured (European-African-Malay) and white women. Frequency of severe nausea ranged from 3.8% in rural blacks to 19.8% in white women, and of severe vomiting from 3.1% in rural blacks to 17.8% in white and Indian women. Proportions in the other groups were intermediate. Pronounced cravings, claimed by 67-84% in the various groups, included sour, savoury and sweet foods, also fruit and milk. Aversions were claimed by 45-81% of the women in the different groups with meat, fish, coffee and fatty foods, the foods most often avoided. Pica, the consumption of such substances as earth, clay, varied ethnically and regionally; frequency was high in rural and urban black women (44.0% and 38.3%), but much lower (5%) in Indian, coloured and white women.

Topics: Adult; Asian People; Black People; Female; Food Preferences; Humans; Nausea; Pica; Pregnancy; Pregnancy Complications; Rural Population; South Africa; Twins; Urban Population; Vomiting; White People

Three interrelated symptom ' complexes' are implicated in dietary changes during pregnancy: nausea and vomiting of pregnancy (NVP), dietary aversions, and dietary cravings. These are discussed with particular emphasis on NVP and the fate of the fetus.

Topics: Diet; Female; Fetus; Food; Food Preferences; Humans; Nausea; Nutritional Requirements; Pica; Pregnancy; Pregnancy Complications; Vomiting