Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various classes of antidepressant drugs with distinct pharmacologic actions are differentially effective in the treatment of classic melancholic depression--characterized by pathological hyperarousal and atypical depression--associated with lethargy, hypersomnia, and hyperphagia. All antidepressant agents exert their therapeutic efficacy only after prolonged administration. In situ hybridization histochemistry was used to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of 3 different classes of activating antidepressant drugs which tend to be preferentially effective in treating atypical depressions, on the expression of central nervous system genes thought to be dysregulated in major depression. Daily administration (5 mg/kg, i.p.) of the selective 5-hydroxytryptophan (5-HT) reuptake inhibitor fluoxetine, the selective alpha 2-adrenergic receptor antagonist idazoxan, and the nonspecific monoamine oxidase A and B inhibitor phenelzine increased tyrosine hydroxylase mRNA levels by 70-150% in the locus coeruleus after 2 weeks of drug and by 71-115% after 8 weeks. The 3 drugs decreased corticotropin-releasing hormone mRNA levels by 30-48% in the paraventricular nucleus of the hypothalamus. The decreases occurred at 8 weeks but not at 2 weeks. No consistent change in steroid hormone receptor mRNA levels was seen in the hippocampus with the 3 drugs, but fluoxetine and idazoxan increased the level of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA, respectively, after 8 weeks of drug administration. Proopiomelanocortin (POMC) mRNA levels in the anterior pituitary and plasma adrenocorticotropic-hormone (ACTH) levels were not altered after 2 or 8 weeks of drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: therapeutic implications. 135 83

The obese Zucker rat (fa/fa) is an animal model for genetic obesity characterized by hyperphagia, hyperinsulinemia, and severe insulin resistance in peripheral tissues. Adrenal steroids seem to play an important role in the onset of fatty syndrome in these animals. There is strong evidence of abnormal regulation of the hypothalamic-pituitary-adrenal axis in obese Zucker rats. Considering the physiological function of arginine vasopressin (AVP) as an adrenocorticotropic hormone secretagogue, the present study was carried out to investigate the role of glucocorticoids in the control of hypothalamic AVP systems in lean and obese Zucker rats. In the first experiment, mifepristone (RU 38486), a glucocorticoid receptor antagonist, was administered for 4 days (10 mg/kg orally twice daily), and the expression of AVP mRNA in hypothalamic paraventricular and supraoptic nuclei was measured using in situ hybridization, and the concentrations of AVP in the pituitary gland and in the median eminence were quantified. Plasma corticosterone levels were also analyzed. Mifepristone treatment resulted in a threefold increase in plasma corticosterone levels in lean Zucker rats, but it did not change corticosterone secretion in obese animals. Mifepristone treatment decreased AVP mRNA levels in lean animals in the supraoptic nuclei, while in obese animals the AVP mRNA content was increased in the paraventricular nuclei. Mifepristone treatment significantly increased the concentration of AVP in the median eminence in lean rats and decreased it in obese animals. Mifepristone treatment did not change concentrations of AVP in the pituitary gland. In the second experiment, mifepristone was given for 4 days (10 mg/kg orally twice daily), and its effects on 24-hour food intake and plasma AVP concentrations were measured.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential hypothalamic arginine vasopressin response to glucocorticoid receptor antagonism in lean and obese Zucker rats. 140 82

Neuropeptide Y (NPY) is an important hypothalamic regulator of feeding behavior. In this study we have investigated the regulation of the expression of preproNPY mRNA in male obese and lean Zucker rats by in situ hybridization. These animals represent a model of genetic obesity with hyperphagia, hyperinsulinemia and altered endocrine functions. Obese Zucker rats, treated for 12 days with 0.9% saline, had about 210% higher level of basal preproNPY mRNA expression in the arcuate nucleus when compared to their lean littermate controls. Repeated administrations of 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), a serotonergic 5-HT1A agonist, or mifepristone, a glucocorticoid receptor antagonist, did not modify the basal expression of preproNPY mRNA in the Zucker phenotypes. The 8-OH-DPAT treatment significantly reduced hyperinsulinemia in obese Zucker rats without changing plasma glucose levels. The mifepristone treatment significantly increased plasma corticosterone levels in lean animals, but not in obese animals. The present study demonstrates enhanced expression of preproNPY mRNA in the arcuate nucleus in obese Zucker rats suggesting an involvement of NPY in the pathophysiology of the hyperphagic syndrome and genetically determined obesity in Zucker rats. Neither the antagonism of glucocorticoid receptors by mifepristone, nor repeated treatment with 8-OH-DPAT resulting in reduced insulin levels in obese Zucker rats, modified the basal expression of preproNPY mRNA in the arcuate nucleus.
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PMID:Effects of repeated administration of mifepristone and 8-OH-DPAT on expression of preproneuropeptide Y mRNA in the arcuate nucleus of obese Zucker rats. 165 93

Both serotonergic dysfunction and glucocorticoid hypersecretion are implicated in affective and eating disorders. The adverse effects of serotonergic (5-HT)2C receptor activation on mood and food intake, the antidepressant efficacy of 5-HT2 receptor antagonists, and the hyperphagia observed in 5-HT2C receptor knockout mice all suggest a key role for increased 5-HT2C receptor-mediated neurotransmission. Glucocorticoids, however, downregulate 5-HT2C receptor mRNA in the hippocampus, and it is unclear how increased 5-HT2C receptor sensitivity is achieved in the presence of elevated glucocorticoid levels in depression. Here we show a monophasic diurnal rhythm of 5-HT2C receptor mRNA expression in the rat hippocampus that parallels time-dependent variations in 5-HT2C receptor agonist-induced behaviors in open field tests. Rats entrained to chronic food restriction show marked but intermittent corticosterone hypersecretion and maintain an unaltered 5-HT2C receptor mRNA rhythm. The 5-HT2C receptor mRNA rhythm, however, is suppressed by even modest constant elevations of corticosterone (adrenalectomy + pellet) or with elevated corticosterone during the daytime (8 A.M.), whereas a normal rhythm exists in animals that have the same dose of corticosterone in the evening (6 P.M.). Thus, animals showing even a transient daytime corticosterone nadir exhibit normal hippocampal 5-HT2C receptor mRNA rhythms, even in the presence of overt corticosterone hypersecretion. Chronic food restriction also abolishes the normal diurnal variation in hippocampal glucocorticoid receptor (GR) and mineralocorticoid receptor mRNAs and produces, unusually, both elevated corticosterone and increased GR. The mismatch between elevated glucocorticoids and maintained 5-HT2C receptor and increased GR gene expression in the hippocampus provides a new model to dissect mechanisms that may underlie affective and eating disorders.
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PMID:Dysregulation of diurnal rhythms of serotonin 5-HT2C and corticosteroid receptor gene expression in the hippocampus with food restriction and glucocorticoids. 915 22

Hypothalamic neuropeptide Y containing neurones are overactive and may mediate hyperphagia in insulin-deficient diabetic rats, but the factors stimulating them remain uncertain. To determine the possible role of glucocorticoids, we investigated the effects of the glucocorticoid receptor blocker mifepristone (RU486) on food intake and regional hypothalamic neuropeptide Y concentrations in streptozotocin-diabetic rats. RU486 (30 mg/kg) or corn oil vehicle control was given orally for 3 weeks to diabetic rats. Food intake and neuropeptide Y levels in the hypothalamic arcuate and paraventricular nuclei were increased in untreated diabetic rat groups (P < 0.01), and though RU486 did increase plasma corticosterone levels (P < 0.01) it did not have any effect on either feeding or neuropeptide Y levels (P = NS). These negative findings suggest that glucocorticoids may not be responsible for increasing hypothalamic neuropeptide Y or for hyperphagia in insulin-deficient diabetes.
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PMID:Increased hypothalamic neuropeptide Y concentration or hyperphagia in streptozotocin-diabetic rats are not mediated by glucocorticoids. 953 19

These studies explored the possibility that glucocorticoids promote parental care in ring doves by mediating, at least in part, the pronounced increase in food consumption that parent doves exhibit while provisioning their young. Plasma concentrations of the endogenous glucocorticoid corticosterone were found to be significantly higher in breeding females during the posthatching phase than during the incubation period. These differences were not observed in male breeding partners, but sex differences in daily activity rhythms are well documented in breeding doves, and blood sampling at different times of day would be required to adequately characterize the pattern of corticosterone in males during these breeding stages. In studies on nonbreeding doves, twice-daily intracerebroventricular (icv) injections of the synthetic glucocorticoid dexamethasone (DEX) increased food intake by 25-50% in both sexes, and further studies in males revealed that the increase was directly related to the dose of DEX administered. The highest dose of DEX given icv (1.0 microg/day) was not effective in stimulating feeding when given systemically, thereby suggesting that the hyperphagic action of DEX is exerted directly on the central nervous system. The icv infusion of the selective glucocorticoid receptor antagonist RU38486 blocked the hyperphagic effects of twice-daily icv injections of DEX in both sexes. Collectively, these data support the hypothesis that corticosterone contributes to the parental hyperphagia exhibited by breeding doves during the posthatching period. They also suggest that these orexigenic effects are mediated in part by CNS binding sites that resemble mammalian glucocorticoid receptors.
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PMID:Glucocorticoids and parental hyperphagia in ring doves (Streptopelia risoria). 1186 79

Plasma corticosterone increases during spring migration in a variety of bird species, including the Gambel's white-crowned sparrow Zonotrichia leucophrys gambelii. Corticosterone is elevated specifically in association with migratory flight, suggesting that corticosterone may promote processes such as energy mobilization and/or migratory activity. General effects of glucocorticoids support such a prediction. Because glucocorticoids exert permissive effects on food intake, corticosterone may also participate in the regulation of migratory hyperphagia. To examine the role of corticosterone during migration, we induced Gambel's white-crowned sparrows to enter the migratory condition and compared food intake and locomotor activity between controls and birds injected with RU486--an antagonist to the low-affinity glucocorticoid receptor (GR). In addition, we investigated effects of RU486 in birds that were subjected to a short-term fast. Results indicate that RU486 did not affect locomotor activity. However, consistent with its effects in mammals, RU486 suppressed food intake. Thus, hyperphagia and migratory restlessness, the two behaviors that characterize migration, may be regulated by different mechanisms. Lastly, RU486 antagonized fasting-induced lipid mobilization, as evidenced by decreased plasma free fatty acids. Thus, data on spring migrants suggest that endogenous corticosterone levels act through the GR to support hyperphagia and that the GR promotes availability of lipid fuel substrates in association with periods of energetic demand, e.g. during migratory flight.
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PMID:The low-affinity glucocorticoid receptor regulates feeding and lipid breakdown in the migratory Gambel's white-crowned sparrow Zonotrichia leucophrys gambelii. 1463 41

Plasma corticosterone increases in association with migratory flight in the red knot Calidris canutus islandica, suggesting that corticosterone may promote migratory activity and/or energy mobilization in this species. This hypothesis is supported by general effects of glucocorticoids, which include stimulation of locomotion and the mobilization of energy depots. We experimentally examined the role of elevated corticosterone levels in the migratory red knot by comparing foraging behavior, flight frequency, and plasma metabolites between vehicle-injected controls and birds treated with RU486, an antagonist to the genomic low-affinity glucocorticoid receptor (GR). We predicted that RU486 treatment would interfere with energy mobilization. However, we expected no effects on flight activity because recent studies suggest that glucocorticoids affect locomotion through a nongenomic receptor. Finally, because glucocorticoids exert permissive effects on food intake, we postulated that RU486 treatment in the red knot would interfere with feeding. Results were consistent with the latter prediction, suggesting that the GR participates in the promotion of hyperphagia, the intense feeding state that is characteristic of the migratory condition. RU486 treatment did not affect flight frequency, suggesting that corticosterone may support migratory activity through a receptor other than the GR. Energy metabolism (as determined through plasma metabolites) was also unaffected by RU486, possibly because energetic demands experienced by captive birds were low.
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PMID:Role of the low-affinity glucocorticoid receptor in the regulation of behavior and energy metabolism in the migratory red knot Calidris canutus islandica. 1544 37

Hyperphagia is a prominent component of the parental behavior repertoire in male and female ring doves and is necessary in order for parents to successfully provision their growing young. Although previous studies implicate both prolactin and the endogenous glucocorticoid, corticosterone, in parental hyperphagia, the functional interactions between these two hormones in regulating changes in feeding activity have not been characterized. These studies examined the possibility that prolactin's orexigenic effects are mediated through the increased secretion of corticosterone. Twice-daily intracerebroventricular (icv) injection of prolactin increased plasma corticosterone concentration in non-breeding doves of both sexes, with males exhibiting more pronounced effects than females. To further test the importance of glucocorticoid signaling in prolactin-induced feeding responses, changes in food intake were investigated in icv prolactin-treated, non-breeding doves following icv infusion of the glucocorticoid receptor antagonist RU38486 or propylene glycol vehicle. No attenuation of prolactin-induced hyperphagia was observed in either sex following co-administration of RU38486 at a dose shown previously to block dexamethasone-induced feeding in doves. These findings suggest that elevated corticosterone titers in blood may contribute to the hyperphagia observed in response to prolactin, but corticosterone signaling through a mammalian-type glucocorticoid receptor is not essential.
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PMID:Prolactin-induced parental hyperphagia in ring doves: are glucocorticoids involved? 1546 37

Chronic leptin administration at pharmacologic doses normalizes food intake and body weight in streptozotocin (STZ)-diabetic rats. We examined the metabolic effects of acute partial physiological leptin restoration in STZ-diabetic rats by using subcutaneous osmotic mini pumps. Groups: (1) Rats infused with vehicle (DV); (2) rats infused with recombinant murine methionine leptin (DL) at 4.5 microg . (kg body weight . d)(-1); (3)pair-fed rats (DP) given a food ration matching that consumed by the DL group. A fourth group of nondiabetic, normal (N) rats was also studied to assess normal metabolic efficiency, hypothalamic-pituitary-adrenal (HPA) activity and sympathoadrenal activity. Following leptin infusion, food consumption by DL rats was significantly lower than in DV rats. Paradoxically, despite a similar food intake to that of the DP group, which demonstrated a 40% reduction in body mass, DL rats increased their initial body weight by approximately 20% (P < .05). Plasma corticosterone and ACTH concentrations were elevated by 2-fold to 3-fold in DL versus N, DP, and DV rats. In the pars distalis, glucocorticoid receptor (GR) mRNA levels were significantly higher in DL and DP rats compared with N and DV rats. Our results suggest that partial restoration of physiologic leptin: (1) successfully reduces hyperphagia while allowing body weight gain in STZ-diabetic rats; (2) increases corticosterone levels in STZ-diabetic rats, which may in turn counteract the anorexic effects of diabetes; and (3) is associated with increased pituitary GR mRNA levels, despite elevated corticosterone levels, suggesting that leptin may interfere with the negative feedback regulation of the HPA axis.
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PMID:Partial leptin restoration increases hypothalamic-pituitary-adrenal activity while diminishing weight loss and hyperphagia in streptozotocin diabetic rats. 1556


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