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

Using microdialysis in freely moving rats, we have been able to observe changes in monoamines from the ventromedial and paraventricular hypothalamic nuclei before, during, and after spontaneous feeding. Because the genetically obese Zucker rat shows abnormalities related both to feeding and monoamines, it was of interest to investigate possible particularities in the monoaminergic variations around spontaneous feeding. The profile of changes in Zucker rats was grossly similar to that of Wistar rats: increases in 5-hydroxy-tryptamine (5-HT), 5-hydroxyindolacetic acid (5-HIAA), and dopamine (DA), and decrease in dihydroxyphenylacetic acid (DOPAC). However, the release in monoamines (5-HT and DA) was more dramatic and longer-lasting than in Wistar rats, while the changes in the metabolites were proportionnally less pronounced. This suggests that high concentrations of these feeding-related amines are released and remain in the synaptic cleft of the obese rat, possibly because they are required in larger amounts to bring about satiety. The hyperphagia of the obese Zucker rat may therefore be the result of a resistance to these prandially released satiety-promoting neurosubstances.
 ...
PMID:Spontaneous feeding-related monoamine changes in rostromedial hypothalamus of the obese Zucker rat: a microdialysis study. 754 69

Drugs, such as sodium mercaptoacetate and methylpalmoxirate, which block fatty acid oxidation at different levels in the metabolic pathway, stimulate feeding. It is well known that selective centrally induced stimulation of dopamine, serotonin (5-hydroxytryptamine, 5-HT) and beta-adrenoceptors, or inhibition of the opiatergic system substantially decrease food intake in rats trained to eat 4 h a day. The results of the present study show that centrally acting dopaminergic and serotoninergic anorectic drugs, the opiate receptor antagonist naloxone, the alpha-adrenoceptor blocking drug phentolamine, and peripherally administered 5-HT counteract the overeating induced by mercaptoacetate. Comparing these effects to those described in 2-deoxy-D-glucose- and insulin-induced feeding, our data support the proposition that distinct neural circuits are involved in the hyperphagic responses to diverse metabolic stimuli.
 ...
PMID:Pharmacological antagonism of lipoprivic feeding induced by sodium mercaptoacetate. 760 Dec 16

The obese Zucker rat is a model of youth-onset obesity associated with hyperphagia. In this study, dehydroepiandrosterone's effect at decreasing food intake and body weight in the obese Zucker rat was investigated. Rats were treated with a dehydroepiandrosterone-supplemented diet (0.0, 0.06, 0.15, 0.3, or 0.6%) for 7 days. The 0.3 and 0.6% treatment groups showed a dramatic decrease in daily food intake, which was evident the 1st day. In addition to the reduction in food intake, body weight changes also were affected significantly in the high-dose treatment groups. The possibility that these dehydroepiandrosterone-induced changes were correlated to perturbations in central neurotransmitter levels associated with appetite control was investigated. The hypothalamus, frontal cortex, striatum, and hippocampus of dehydroepiandrosterone-treated animals were assayed for neurotransmitters known to have inhibitory or stimulatory effects on feeding behavior (serotonin, dopamine, norepinephrine, and epinephrine). Significant differences from steroid-free controls were noted only in the levels of hypothalamic serotonin in animals treated with dehydroepiandrosterone. Serotonin in the hypothalamus has been shown to decrease feeding behavior. The magnitude of dehydroepiandrosterone's effect on hypothalamic serotonin correlated with its effect on feeding behavior. Thus, dehydroepiandrosterone may reduce hyperphagia by altering hypothalamic levels of serotonin.
 ...
PMID:Effect of dehydroepiandrosterone on neurotransmitter levels and appetite regulation of the obese Zucker rat. The Obesity Research Program. 768 87

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.
 ...
PMID:Brain serotonin depletion attenuates diabetogenic effects of streptozotocin. 776 35

d-Fenfluramine (0.63 mg/kg i.p.), a serotonin (5-hydroxytryptamine, 5-HT) releaser and re-uptake inhibitor, reduced the eating caused by neuropeptide Y (235 pmol) injected into the paraventricular nucleus of the hypothalamus. The 5-HT1 and 5-HT2 receptor antagonist metergoline (1.0 and 2.0 mg/kg i.p.) and the 5-HT1A and 5-HT1B receptor antagonist (+/-)-cyanopindolol (3.0 and 8.0 mg/kg s.c.) significantly antagonized the effect of d-fenfluramine. The 5-HT2A and 5-HT2C receptor antagonist mesulergine (0.1 and 0.3 mg/kg s.c.) and the 5-HT2A receptor antagonist ketanserin (2.5 and 5.0 mg/kg i.p.) did not significantly modify the effect, nor did the 5-HT1A and 5-HT1B receptor antagonist (-)-propranolol (20-40 nmol), injected bilaterally into the paraventricular nucleus of the hypothalamus. The results suggest that d-fenfluramine reduces neuropeptide Y's hyperphagia by indirectly stimulating 5-HT1B receptors outside the paraventricular nucleus of the hypothalamus.
 ...
PMID:The 5-HT1B receptor mediates the effect of d-fenfluramine on eating caused by intra-hypothalamic injection of neuropeptide Y. 776 74

Treadmill exercise (1 h at 20 m/min) has been shown to increase brain serotonin (5-HT) synthesis/metabolism in 4-day trained rats. This work has analysed whether these changes are associated with (5-HT-dependent or -independent) alterations in pre- and postsynaptic 5-HT1A receptor-mediated behaviours; in addition, the controversial hypothesis that exercised rats are less anxious than sedentary rats was tested in the elevated plus-maze and the social interaction models. Acute administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.125-0.5 mg/kg) triggered hyperphagia, forepaw treading, and flat body posture, the amplitude of which were not affected by training or acute exercise. In the elevated plus-maze, training, but not acute exercise, reduced the number of total arm entries. In the social interaction test, trained and acutely exercised rats displayed increased locomotion and decreased defecation, compared to resting rats, but social interaction and rearings were not affected. It is suggested that the aforementioned effects of acute exercise upon 5-HT synthesis/metabolism in short-term trained rats are not associated with changes in 5-HT1A receptor- and anxiety-related behaviours.
 ...
PMID:Influence of physical exercise on 5-HT1A receptor- and anxiety-related behaviours. 783 Sep 52

Functional interactions between serotonergic (5-HT) and opioid drugs have been observed with 5-HT3 receptor antagonism enhancing the inhibitory actions of naloxone and naltrexone in both food-deprived and glucoprivic rats; 5-HT2A/C receptor antagonism enhanced naltrexone's inhibition of insulin hyperphagia. The present study examined whether pretreatment with either general 5-HT (methysergide: 0.5-5 mg/kg), 5-HT2A/C (ritanserin: 0.25-2.5 mg/kg), or 5-HT3 (ICS 205930: 0.5-5 mg/kg) antagonists altered the pattern and magnitude of ad lib intake of simple (sucrose: 10%) or more complex (maltose dextrin: MD, 10%) carbohydrate solutions, or naltrexone's (0.25-2.5 mg/kg) inhibition of these forms of intake. Methysergide significantly increased the pattern and magnitude of sucrose intake at low (0.5-2.5 mg/kg) doses, and transiently delayed the pattern of MD intake at high (5 mg/kg) doses. Ritanserin significantly accelerated the pattern, but not the magnitude of sucrose intake at low (0.25-1.25 mg/kg) doses without affecting MD intake. ICS 205930 reduced the magnitude of sucrose intake at the highest (5 mg/kg) dose, and transiently reduced MD intake. Naltrexone dose dependently altered the pattern and magnitude of both sucrose and MD intake. Coadministration of ritanserin and naltrexone either eliminated or delayed the pattern of opioid antagonist inhibition of both sucrose and MD intake. Methysergide and ICS 205930 pretreatment produced minor changes in the pattern of naltrexone-induced inhibition. These data indicate that 5-HT receptor differentially modulate the pattern of carbohydrate intake, and indicate differential ingestive interactions between 5-HT and opioid antagonists under challenge and palatable conditions.
 ...
PMID:Naltrexone, serotonin receptor subtype antagonists, and carbohydrate intake in rats. 802 91

d-Fenfluramine is a 5-HT agonist which decreases food intake and excessive carbohydrate intake in humans. A placebo-controlled trial of d-fenfluramine (45 mg/day) was conducted in 43 patients with bulimia nervosa. The patients entered an eight-week trial of medication during which they also received cognitive-behavioural therapy. Treatment response was assessed using food diaries to record eating behaviour, and self-rating questionnaires to measure psychopathology. The drug trial, and a follow-up assessment after a further eight weeks, were completed by 39 patients. Abnormal eating behaviour and psychopathology improved significantly in both the d-fenfluramine and placebo groups during the treatment trial. The study failed to show that the addition of d-fenfluramine affords an advantage over brief psychotherapy alone. Although d-fenfluramine is effective in suppressing the overeating, excessive snacking, and excessive carbohydrate consumption which are frequently found in overweight or obese patients, this study suggests that the drug is not an effective treatment for bulimia nervosa.
 ...
PMID:A placebo-controlled trial of d-fenfluramine in bulimia nervosa. 825 96

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.
 ...
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

The anxiolytic property of R-(+)-8-OSO2CF3-PAT(R-(+)-8- [[(trifluoromethyl)sulfonyl]oxy]-2-(n-propyl-amino)tetralin), a 5-HT1A receptor agonist, was evaluated in Wistar rats by means of animal models of anxiety, the conditioned defensive burying model and the conditioned stress-induced freezing response followed by the elevated plus-maze test, respectively. In addition, the 5-HIAA/5-HT ratio (5-hydroxy-indole acetic acid/5-hydroxytryptamine) of rat brain homogenates was studied. Acute drug administration resulted in abolition of the burying behaviour (3 mg/kg i.p.), a dose-dependent decrease of rearing and induction of hyperphagia. R-(+)-8-OSO2CF3-PAT had no effect on conditioned footshock-induced freezing behaviour but increased open-arm activity in the rats on the plus-maze. The 5-HIAA/5-HT ratio was decreased in the lateral septum (1 and 3 mg/kg), dorsal hippocampus (3 mg/kg) and somatosensory cortex (3 mg/kg), implying that R-(+)-8-OSO2CF3-PAT affects particularly the limbic system in anxiety-inducing situations.
 ...
PMID:Potential anxiolytic properties of R-(+)-8-OSO2CF3-PAT, a 5-HT 1A receptor agonist. 866 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>