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)

Two experiments examined the possibility that mice rendered obese by systemic injection of goldthioglucose (GTG) possess altered endogenous levels of brain norepinephrine (NE), dopamine (DA), serotonin (5-hydroxytryptamine or 5HT) and/or 5-hydroxyindoleacetic acid (5HIAA). In the first experiment, single-housed GTG-obese mice were found to have normal brain DA and 5HIAA but 14% less NE and 6% less 5HT than controls. This neurochemical profile was strikingly similar to that previously reported for rats rendered obese by ventromedial hypothalamic lesions (i.e., normal DA and 5HIAA, 19% less NE, 7% less 5HT). However, in the second experiment, equally obese GTG mice pair-housed with non-obese controls showed normal DA, 5HIAA, and NE but 9% more 5HT than controls. In other words, absolute levels of these brain substances were inconsistent with respect to obesity across experiments. On the other hand, when ratios of all possible combinations of these compounds were compared across experiments, only 5HT/NE ratios were consistently different (higher) in GTG mice. In addition, reliable inverse correlations were obtained between weight gain parameters and brain 5HT/NE or 5HIAA/NE ratios for GTG mice. These findings suggest that interactions between brain 5HT and NE neurons may contribute to the overeating and obesity which occur in mice after GTG administration.
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PMID:Association of altered brain norephinephrine and serotonin with the obesity induced by goldthioglucose in mice. 36 Feb 29

Although characterized as hypothyroid, streptozotocin-diabetic rats have reduced serotonin turnover (5-hydroxyindoleacetic acid/serotonin, 5-HIAA/5-HT) in brain stem, while hypothyroid rats have increased 5-HIAA/5-HT. In the present study the two treatments were combined to determine if they affected 5-HIAA/5-HT through the same mechanism. In addition, an alternative method was used to assess 5-HT activity in thyroidectomized (TX) rats, i.e. measurement of 5-HT disappearance after inhibition of tryptophan hydroxylase with p-chlorophenylalanine (PCPA). Adult male rats were first TX (experiment 1) or given methimazole (METH; experiment 3). Two weeks later, diabetes (DB) was induced with streptozotocin in hypothyroid rats and euthyroid controls. Two weeks later, functional measurements were taken. Rats were then killed, and spinal cord and brain stem serotonin turnover (5-HIAA/5-HT), as well as plasma T3, T4 and corticosterone (CORT) concentrations were measured. TX attenuated diabetic hyperphagia and weight loss. DB alone led to moderate reductions in T3 and T4, but the hormones were barely detectable in plasma of TX and METH rats. CORT was elevated in DB but was not affected by TX. Open field activity was not affected by DB or TX. TX and METH significantly increased 5-HIAA/5-HT in both spinal cord and brain stem. TX also led to enhanced disappearance of 5-HT after PCPA. DB significantly reduced 5-HIAA/5-HT, suggesting independent effects of the treatments. However, DB-TX rats still had significantly higher 5-HIAA/5-HT than control-sham surgery rats, while DB-METH rats had 5-HIAA/5-HT indistinguishable from controls. In both cases, prior induction of primary hypothyroidism interfered with the expected diabetes-induced reduction in 5-HT turnover.
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PMID:Streptozotocin-induced decreases in serotonin turnover are prevented by thyroidectomy. 127 45

In rats with microdialysis probes in the perifornical lateral hypothalamus (PFH) a single injection of the D2 receptor blocker 1-sulpiride (20 mg/kg IP) significantly increased extracellular dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), but not 5-hydroxyindoleacetic acid (5-HIAA). This suggests that sulpiride crosses the blood-brain barrier and blocks D2 dopamine receptors in the PFH leading to increased dopamine turnover reflected in increased extracellular DOPAC and HVA. We conclude that D2 blockade in the hypothalamus could play a role in the hyperphagia and body weight gain observed in female rats under chronic administration of the antipsychotic drug, sulpiride.
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PMID:Systemic sulpiride increases dopamine metabolites in the lateral hypothalamus. 170 61

Genetically obese Zucker rats are hyperphagic, hyperinsulinemic and hyperlipemic. In order to investigate pathophysiological mechanisms underlying hyperphagia in these animals, monoamine metabolism and turnover were studied in discrete hypothalamic nuclei known to participate in the control of feeding behavior. Neurochemical studies in genetically obese Zucker rats and in their lean littermate controls were complemented by investigating feeding behavioral responses to the acute administration of clonidine (15 and 30 micrograms/kg i.p.), an alpha 2-adrenoceptor agonist, and to trifluoromethylphenylpiperazine (TFMPP; 1, 2 and 5 mg/kg s.c.), a putative serotonergic 5-hydroxytryptamine-1B receptor agonist. Obese Zucker rats had significantly lower concentrations of 5-hydroxyindoleacetic acid, the main deaminated metabolite of 5-hydroxytryptamine, in the nucleus paraventricularis (PVN) and in the nucleus ventromedialis (VMN), when compared to their lean littermate controls. The rate of accumulation of 5-hydroxytryptophan after decarboxylase inhibition was reduced in the PVN, nucleus supraopticus, nucleus periventricularis and nucleus suprachiasmaticus of the obese rats. No differences were observed in basal concentrations of norepinephrine, dopamine or 3,4-dihydroxyphenylacetic acid between obese and lean Zucker rats in the brain areas studied. However, the rate of accumulation of 3,4-dihydroxyphenylalanine was lower in the VMN and in the median eminence of the obese rats. The feeding behavioral tests showed significantly augmented hyperphagic responses to clonidine in obese Zucker rats. The anorexic effect of TFMPP was similar in both phenotypes. It is concluded that serotonergic activity is reduced in obese Zucker rats, particularly in the PVN, which plays a key role in the control of feeding behavior. The reduced serotonergic activity may be associated with enhanced alpha 2-adrenoceptor-mediated feeding responses in obese Zucker rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothalamic neurochemistry and feeding behavioral responses to clonidine, an alpha-2-agonist, and to trifluoromethylphenylpiperazine, a putative 5-hydroxytryptamine-1B agonist, in genetically obese Zucker rats. 198 Jul 23

There is evidence for reciprocal interactions between the brain monoamine neurotransmitters serotonin and noradrenaline which may play a critical role in homeostasis. The aim of the present study was to establish the effect of drug-induced damage to the serotoninergic system on noradrenergic activity in the hypothalamus. Bilateral intracerebroventricular injections of p-chlorophenylalanine (PCPA; 3 mg/kg in 2 x 6 microliters) were made to induce destruction in the serotoninergic system. Relative to saline-injected controls, PCPA-injected rats began overeating by 3 days postinjection. On day 10, when the experimental rats were consuming approximately 120% that of controls, animals were 4-h food deprived, sacrificed and the medial basal hypothalamus was removed for later analysis (by gas chromatography/mass spectrometry) of noradrenaline (NA), serotonin (5-HT) and dopamine (DA) and their principal metabolites dihydroxyphenylethyleneglycol (DHPG), 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC), respectively. The ratio of metabolite to monoamine provided an index of functional activity. Trunk blood was collected for analysis of serum insulin and glucose. PCPA-injected animals had higher levels of DHPG (P less than 0.05), an increase in the DHPG/NA ratio (P less than 0.02), lower serum insulin (P less than 0.05) and increased serum glucose (P less than 0.05). There were significant correlations between noradrenergic activity (DHPG/NA ratio) and: (1) food intake (day 9 and 10 average; r = 0.62, P less than 0.05); and (2) serum glucose (r = 0.59, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Medial basal hypothalamic monoamine activity associated with intracerebroventricular p-chlorophenylalanine-induced hyperphagia. 214 5

The effects of para-chlorophenylalanine pre-treatment (PCPA, 150 mg/kg IP daily for 3 days) on feeding and stereotyped behaviour elicited by the serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in rats were investigated. PCPA depleted brain serotonin and 5-hydroxyindoleacetic acid concentrations by 90% and increased feeding during a 2-h day-time test. 8-OH-DPAT (60-4000 micrograms/kg SC) increased food intake in control animals but decreased it in PCPA-treated animals during the 2-h test. PCPA treatment had no effect on 8-OH-DPAT-induced locomotion or serotonin-related stereotyped behaviour (i.e. forepaw treading, headweaving, wet dog shakes, etc). Since PCPA prevents the operation of pre-synaptic serotonergic mechanisms, the failure of 8-OH-DPAT to increase food intake in PCPA-treated rats suggests that 8-OH-DPAT-induced hyperphagia is autoreceptor mediated.
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PMID:Para-chlorophenylalanine prevents feeding induced by the serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). 242 76

The present study was undertaken to investigate the hyperphagic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in young and adult rats fed either a powder diet or pellets. In the young rats, 8-OH-DPAT (500 micrograms/kg s.c.) increased the consumption of pellets--but not powder--during the 2 h following drug administration. On the other hand, 8-OH-DPAT did not promote hyperphagia in adult rats presented with either pellets or a powdered diet. The influence of the 5-HT1A agonist on midbrain serotonin (5-hydroxytryptamine, 5-HT) turnover was examined. Administration of 8-OH-DPAT (500 micrograms/kg s.c.) induced similar decreases in 5-HT turnover, as reflected by the ratio of 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT, in young and adult rats 1 h after administration. Nevertheless, some metabolic responses to 8-OH-DPAT were found to be influenced by age. Young and adult rats were injected with a low dose of 8-OH-DPAT (50 micrograms/kg s.c.) to specifically test the presynaptic regulation of 5-HT turnover. Again, midbrain 5-HIAA to 5-HT ratios were decreased to the same extent in both young and adult rats. The results suggest that (i) gnawing may be an important parameter in the food consumption that is triggered by a high dose of 8-OH-DPAT, (ii) analysis of the presynaptic effects of 8-OH-DPAT on 5-HT turnover cannot solely explain the influence of the agonist on feeding behavior.
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PMID:Feeding responses to a high dose of 8-OH-DPAT in young and adult rats: influence of food texture. 245 45

Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A) was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled overeating episodes are accompanied by purging activities and extreme concerns about body shape and weight. The following indices were measured: plasma and urinary phenylacetic acid (PAA), homovanillic acid (HVA), vanillylmandellic acid (VMA); plasma tryptamine (T), beta phenylethylamine (PE), and 5-hydroxyindoleacetic acid (5-HIAA) and urinary 6-sulphatoxymelatonin (aMT6s). PE levels remained the same but T showed a trend toward elevation over time. Twenty-four hour levels of urinary aMT6s in BN patients were higher at week 4 when compared to baseline and week 8. There was a significant reduction in plasma VMA and HVA over time during treatment with brofaromine and both plasma HVA and VMA were significantly lower for the brofaromine group compared to placebo at week 4. Plasma 5-HIAA was significantly higher for the brofaromine group after 8 weeks when compared to placebo. Urinary VMA decreased significantly from baseline to week 4 with a partial elevation at 8 weeks. Urinary VMA was also significantly lower in patients on brofaromine at week 4. This study verifies that brofaromine complies with predicted MAO-A inhibiting patterns in a clinical population.
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PMID:Effects of chronic brofaromine administration on biogenic amines including sulphatoxymelatonin and acid metabolites in patients with bulimia nervosa. 750 90

We previously reported lower ventromedial hypothalamic nucleus (VMN) serotonergic activity in 11-wk genetically obese vs. lean Zucker rats. To determine whether the activity was secondary to metabolic alterations associated with this established obesity (e.g., significant hyperphagia and hyperinsulinemia), we examined monoaminergic activity in various brain nuclei of 12-day lean (Fa/Fa and Fa/fa) and obese (fa/fa) rats early in the development of obesity. Obese pups had greater percent carcass fat than heterozygotes, both of which were fatter than homozygous lean rats. Obese, but not heterozygous lean, pups were hyperinsulinemic vs. Fa/Fa pups. VMN 5-hydroxy-3-indoleacetic acid levels, an index of serotonin release, were lower in obese and heterozygous than in homozygous lean pups and were not correlated with plasma insulin levels. Although monoamine differences also occurred in several other nuclei, for the most part they appeared to be unrelated to the obese genotype. We conclude that blunted VMN serotonergic activity is not secondary to the obese rat's hyperinsulinemia and may play a significant role in the development of obesity.
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PMID:Serotonergic activity is depressed in the ventromedial hypothalamic nucleus of 12-day-old obese Zucker rats. 752 10

Thyroid disease is common, and its effects on the gastrointestinal system are protean, affecting most hollow organs. Hashimoto disease, the most common cause of hypothyroidism, may be associated with an esophageal motility disorder presenting as dysphagia or heartburn. Dyspepsia, nausea, or vomiting may be due to delayed gastric emptying. Abdominal discomfort, flatulence, and bloating occur in those with bacterial overgrowth and improve with antibiotics. Reduced acid production may be due to autoimmune gastritis or low gastrin levels. Constipation may result from diminished motility, leading to an ileus, megacolon, or rarely pseudoobstruction. Ascites in myxedema is characterized by a high protein concentration. Graves' disease accounts for 60% to 80% of thyrotoxicosis. Hyperthyroidism is accompanied by normal gastric emptying with low acid production, partly due to an autoimmune gastritis with hypergastrinemia. Transit time from mouth to cecum is accelerated, resulting in diarrhea. Steatorrhea is due to hyperphagia and stimulation of the adrenergic system. Diarrhea in medullary carcinoma of the thyroid (MCT) may be due to elevated calcitonin, prostaglandins, or 5-hydroxyindoleacetic acid. Ileal or colonic function may be abnormal. The esophagus may be compressed by benign processes, but more often by malignancies. MRI and CT scans are the best diagnostic modalities. The gastrointestinal manifestations of thyroid disease are generally due to reduced motility in hypothyroidism, increased motility in hyperthyroidism, autoimmune gastritis, or esophageal compression by a thyroid process. Symptoms usually resolve with treatment of the thyroid disease.
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PMID:The thyroid and the gut. 2035 69


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