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)

Changes in hypothalamic monoamine metabolism were investigated in freely moving streptozotocin (STZ)-induced diabetic rats by using in vivo microdialysis technique. Six weeks later, the animals were implanted with microdialysis probe (molecular weight cut-off index: 12,000-14,000) into the ventromedial portion of the hypothalamus (VMH). The dialysate was collected and loaded onto HPLC to be assayed for norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites (MHPG, DOPAC and 5-HIAA). The concentration of NE was decreased in the dialysate from the VMH of diabetic rats, whereas there was no significant change in MHPG level. The concentrations of 5-HT and 5-HIAA were reduced in diabetic rats. The DA concentration was obviously increased accompanied by the reduction of DOPAC level. The observed changes in hypothalamic monoamine metabolism, especially the reduced NE release, may play an important role in the induction of hyperphagia in freely moving STZ-induced diabetic rats.
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PMID:Alteration in hypothalamic monoamine metabolism of freely moving diabetic rat. 176 95

This minireview deals with the possible roles of monoamines in feeding and feeding disorders. The introduction sketches the results of earlier studies with local drug injections and selective neurotoxins which provided pharmacological evidence that monoamines can influence food intake and body weight. A table summarizing this evidence is used to list monoamine changes that could underlie anorexia or hyperphagia. It is apparent that abnormalities in the monoamines, along with their cotransmitters, could cause many forms of feeding disorder. It is proposed as a working hypothesis that several varieties of hyperphagia leading to obesity have a common element. This common factor is a change in excitability of a lateral hypothalamic reinforcement system as manifested in self-stimulation at a stimulation-bound feeding site. Understanding this feeding reward-aversion system helps us understand hyperphagia and anorexia. The neurochemistry of reward and aversion involves the monoamines. This paper focuses on dopamine and serotonin. The data support the hypothesis that dopamine systems projecting to the nucleus accumbens and other forebrain areas from the mid-brain ventral tegmental area (VTA) are important for approach and positive reinforcement in ingestive behavior and self-stimulation. Serotonin is hypothesized to facilitate satiety and inhibition of feeding reward in the hypothalamus. The next section abstracts our recent experiments that measured pharmacological and physiological release of the monoamines in the hypothalamus and nucleus accumbens during ingestive behavior and self-stimulation. In vivo microdialysis in freely moving rats suggested the following: (1) Norepinephrine was released in the paraventricular nucleus during the active, feeding period of the circadian cycle. (2) The serotonin metabolite 5-HIAA also increased in the PVN at the same time if there was food to eat. (3) Amphetamine infused into the lateral hypothalamus (LH) by reverse dialysis increased synaptic dopamine, norepinephrine, and serotonin. (4) The anorectic drug d-fenfluramine increased synaptic serotonin in the LH and also increased the dopamine metabolite DOPAC, suggesting that serotonin and dopamine in the LH might contribute to fenfluramine-induced satiety. Local d-fenfluramine injection into the LH or local infusion by reverse dialysis again increased serotonin and decreased 5-HIAA and interfered with local dopamine metabolism as reflected in decreased DOPAC and HVA. (5) Tryptophan, a serotonin precursor, given systemically at an anorectic dose, increased extracellular serotonin in the LH, but this effect was only detectable in food-deprived rats. This was seemingly pH independent (between 5.8 and 8). The passage other cations through CFo is strictly suppressed (even at pH 8 and with 300 mM NaCl in the medium).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Microdialysis studies of brain norepinephrine, serotonin, and dopamine release during ingestive behavior. Theoretical and clinical implications. 269 87

We have shown previously that intravenous infusions of insulin, known to induce glucoprivic hunger, and of insulin combined with glucose, known to induce satiety, produce in the VMH and PVN of Wistar rats monoaminergic changes that differ from those related to spontaneously occurring hunger and satiety, while the genetically obese Zucker rat is totally resistant to the behavioural effects of insulin and insulin + glucose infusions. In the present study, the impact of these infusions on VMH and PVN monoamines in obese Zucker rats was assessed using microdialysis. Monaminergic changes (increase in DOPAC and 5-HIAA and decrease in DA and 5-HT) were quite similar in obese rats to those we found in normal rats when insulin was infused. In contrast, changes in 5-HT or DA in response to insulin and glucose were quite different in the Zucker rat. Monoaminergic changes related to meals were more dramatic in the Zucker rat and so were able to reverse the background changes produced by the insulin infusion. These data confirm the idea that the effect on monoamines of spontaneously occurring hunger and satiety is different from the effect on monoamines by insulin and glucose-induced hunger and satiety. The results show disturbances of the obese Zucker rat related both to insulin and to hypothalamic monoamines that may be involved in the hyperphagia and obesity of this model.
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PMID:Rostromedial hypothalamic monoamine changes in response to intravenous infusions of insulin and glucose in freely feeding obese Zucker rats: a microdialysis study. 866 29

1. The effects of mesulergine, a 5-hydroxytryptamine (5-HT) receptor antagonist with dopamine (DA) agonistic properties, on rats diet selection over a seven day period and on 5-HT and DA turnover was studied. 2. Three groups of male Wistar rats were individually caged and ad libitum fed with a standard (SD) and 50% sweet carbohydrate enriched diet (CED). Food intake was measured daily 4 hrs and 24 hrs after i.p. injections of mesulergine (1 and 3 mg/kg) or vehicle. 5-HT and 5-HIAA in hypothalamus (Hy), Striatum (St) and hippocampus (Hi) as well as DA and DOPAC in (Hy) and (St) were assayed at the 8th day of the experiment. 3. There was a dose dependent increase of SD consumption 4 hrs after mesulergine treatment while the CED remained unchanged with total food intake dose dependently increased as a consequence. At 24 hrs measurements SD consumption was increased only for the dose of 1 mg/kg of mesulergine, while a dose dependent decrease of CED intake was observed. Total food intake was unchanged for the dose of 1 mg/kg and decreased with the dose of 3 mg/kg consequently. A dose dependent decrease of rats body weight was observed too. 4. A significant increase of 5-HIAA/5-HT ratio in (Hy) and (St) for the dose of 1 mg/kg and in (Hi) for the dose of 3 mg/kg with no changes of DA turnover were found. 5. The above data suggest a dual mode of action of mesulergine presented as a short term hyperphagia due to simultaneous antiserotonergic and dopaminergic activity and long-term hypophagia due to long-term agonistic effects of dopaminergic neurons.
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PMID:Effects of mesulergine treatment on diet selection, brain serotonin (5-HT) and dopamine (DA) turnover in free feeding rats. 972 21

Pharmacological, neurochemical, and behavioral techniques were used to characterize DA-ACh interaction within the lateral hypothalamus (LH) in the context of locomotion, feeding behavior, and reinforcement. In Experiment 1, the muscarinic agonist carbachol injected in the LH increased locomotor activity in proportion to dose. In Experiment 2, the same doses of carbachol proportionately increased exctracellular DA in the nucleus accumbens (Nac) as monitored by brain microdialysis. Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) also increased. In Experiment 3, LH infusion by reverse microdialysis of the D(2) receptor blocker sulpiride released ACh in the LH in a dose-response manner. This suggested that sulpiride disinhibits ACh release via D(2) receptors in the LH and thereby facilitates behavior. Confirming this in Experiment 4, local LH atropine 5 min before sulpiride suppressed the locomotor response to sulpiride for about 20 min. These results suggest that sulpiride acts in the LH by disinhibiting a hypothalamic locomotor mechanism that is cholinergically driven and connected with the mesoaccumbens dopamine pathway. Given prior results that local sulpiride in the LH can induce hyperphagia and reward, this system may be involved in searching for food and rewarding feeding behavior. In conclusion, DA acts in the LH via D(2) receptors to inhibit cholinergic neurons or terminals that are part of an approach system for eating.
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PMID:Dopamine-acetylcholine interaction in the rat lateral hypothalamus in the control of locomotion. 1088 Jun 73