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)

The present study attempted to replicate and extend two recent studies that implicated aberrant brain 5-HT neurotransmission in the etiology of overeating and BW grain. Adult female rats received 25 mg/kg of desipramine hydrochloride 30--45 min prior to an intracisternal injection of 200 microgram (free base) of 5,7-DHT creatinine sulfate or its 1% ascorbic acid aqueous vehicle. After 7 weeks of measuring food intake, water intake, and BW change, rats from both groups received radiofrequency lesions of the MH or sham surgery. After 5 additional weeks of intake and BW measurements, all rats were tested for 24-hr acceptance of varying sucrose and quinine solutions and for 25-day acceptance of a high-fat replacement diet. While 5,7-DHT depleted brain 5-HT by 45%, it did not induce overeating and BW gain alone nor did it modify the overeating, obesity, or "finickiness" produced by hypothalamic injury. Several factors that relate to specificity, sufficiency, and compatibility with other 5-HT depletory techniques were discussed, as were factors of similarity and dissimilarity between this and the previous experiments that we attempted to replicate.
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PMID:Effects of central 5,7-dihydroxytryptamine on the medical hypothalamic syndrome in rats. 28 Feb 59

A variety of evidence has led to suggestions that brain serotonin (5-HT) and norepinephrine (NE) interact within the medial hypothalamus to control food intake. To test the possibility that chronic decrements in 5-HT might enhance NE-induced feeding, adult male rats were prepared with permanently indwelling cannulae aimed at the paraventricular nucleus (PVN), then received either intracisternal (IC) or PVN injections of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) vs. its vehicle, 1% ascorbic acid. Over a 4-week period, IC-5,7-DHT rats showed no signs of enhanced daily feeding or drinking. However, in 40-min intake tests, feeding but not drinking was enhanced by injecting 20 nmol NE into the PVN commencing 2 weeks after neurotoxin treatment. Terminal monoamine assays confirmed that IC-5,7-DHT produced large (80-90%) depletions of brain regional 5-HT. A functional index of 5-HT terminal damage was also implied by the impaired short-term feeding responses IC-5,7-DHT rats showed to the systemic administration of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) when tested between 3 and 4 weeks after IC treatment. Over a comparable 4-week period, PVN-5,7-DHT rats also showed no tendencies to overeat or overdrink on a daily basis. However, in contrast to IC-5,7-DHT rats, they also showed no differences in their feeding or drinking responses to NE injections into the PVN. This was so despite reliable depletions of 5-HT in the hypothalamus (-28%) and hippocampus (-71%). These results support earlier work showing that neither widespread nor localized hypothalamic damage to brain 5-HT neurons produce chronic overeating. However, the data suggest that phasic enhancements of PVN NE activity may trigger enhanced feeding when there is widespread damage to brain 5-HT neurons, although the PVN does not appear to be the brain site mediating this effect.
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PMID:Effects of intracisternal vs. intrahypothalamic 5,7-DHT on feeding elicited by hypothalamic infusion of NE. 147 2

Long-term changes in food and water intake, body weight, and skeletal growth were assessed following bilateral hypothalamic microinfusions of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). The analysis of ingestive behavior included assessment of photoperiodic effects and responsivity to alterations in dietary composition. The neuroanatomical and neurochemical selectivity of the serotonergic depletion was documented by regional spectrofluorometric analysis for serotonin, dopamine, and norepinephrine. The results indicated that norepinephrine and dopamine were not depleted in the brain areas examined. However, substantial depletion of serotonin occurred in the septum, hippocampus, and hypothalamus of the 5,7-DHT (12 microgram) group. During feeding of a high-fat diet, the serotonin-depleted group exhibited a long-lasting and stable hyperphagia which led to an increase in body weight. This hyperphagia occurred during both phases of the photoperiod but was disproportionately distributed, occurring to a greater extent in the light phase. Because body weight increased in the absence of increased skeletal growth or intestinal weight, it is concluded that the increased body weight reflected increased adiposity. The serotonin-depleted group also exhibited an essential light-phase hyperdipsia, increasing water intake above that which would be accounted for by the light-phase hyperphagia. Because the light-phase hyperdipsia was counterbalanced by a dark-phase hypodipsia, there was no change in the 24-hour water intake. The hyperphagia exhibited by the 5,7-DHT (12 microgram) group was associated with both hippocampal and hypothalamic serotonergic depletion. The results of this investigation provide the first clear evidence of an inhibitory role of serotonin in food intake and point to the importance of maximizing both neurochemical and neuroanatomical selectivity in such investigations.
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PMID:Increased food intake, body weight, and adiposity in rats after regional neurochemical depletion of serotonin. 725 49

The diabetogenic effects of streptozotocin (STZ) were studied on blood glucose, plasma insulin, feeding and drinking, body weight, islet morphology, and hypothalamic serotonin (5-HT) release in vehicle-pretreated rats and in rats pretreated with either intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT; a 5-HT nerve fiber depletor), intraperitoneal injection of p-chlorophenylalanine (PCPA; a tryptophan hydroxylase inhibitor), or intraperitoneal injection of p-chloroamphetamine (PCA; a neurotoxin for 5-HT nerve fiber). At four days after STZ administration, vehicle-treated rats displayed hyperglycemia, polydipsia, polyphagia, decreased plasma insulin level, derangement of islet morphology (few insulin cells, accumulation of glucagon cells), and elevated 5-HT release in the hypothalamus. The above diabetogenic effects of STZ were attenuated by brain serotonin depletion induced by 5,7-DHT, PCPA, or PCA. Furthermore, the STZ-induced hyperglycemia or derangement of islet morphology was attenuated by peripheral sympathectomy or adrenalectomy. It is concluded that brain serotonin depletion attenuates diabetogenic effects of STZ by reducing sympathetic efferent activity in rats.
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PMID:Brain serotonin depletion attenuates diabetogenic effects of streptozotocin. 776 35