Studies on the role of serotonin receptor subtypes in the effect of sibutramine in various feeding paradigms in rats.

Article date: 1999/8/24

PubMed ID: 686171

Journal name: British journal of pharmacology (ISSN: 0007-1188)


The effect of the 5-hydroxytryptamine (5-HT) and noradrenaline (NA) reuptake inhibitor sibutramine was studied in food deprived, neuropeptide Y (NPY)- or muscimol-injected rats. Sibutramine dose-dependently reduced feeding caused by food-deprivation (ED50 = 5.1+/-0.8 mg kg(-1)) or by NPY injection into the paraventricular nucleus of the hypothalamus (ED50 = 6.0+/-0.5 mg kg(-1)). The increase in food intake caused by muscimol injected into the dorsal raphe was not modified by sibutramine (1-10 mg kg(-1)). The hypophagic effect of 5.1 mg kg(-1) sibutramine in food-deprived rats was studied in rats pretreated with different serotonin receptor antagonists. Metergoline (non-selective, 0.3 and 1.0 mg kg(-1)), ritanserin (5-HT2A/2C, 0.5 and 1.0 mg kg(-1)) and GR127935 (5-HT1B/1D), 0.5 and 1.0 mg kg(-1)) did not modify the hypophagic effect of sibutramine, while SB206553 (5-HT2B/2C, 5 and 10 mg kg(-1)) slightly but significantly reduced it (Fint(2.53) = 3.4; P<0.05). The reduction in food intake caused by 6.0 mg kg(-1) sibutramine in NPY-injected rats was not modified by GR127935 (1.0 mg kg(-1)). The results suggest that, with the possible exception of a partial involvement of 5-HT2B/2C receptors in sibutramine's hypophagia in food-deprived rats, 5-HT1 and 5-HT2 receptor subtypes do not play an important role in the hypophagic effect of sibutramine, at least in the first 2 h after injection.

Author List: Grignaschi G, Fanelli E, Scagnol I, Samanin R

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Appetite Depressants; Cyclobutanes; Neuropeptide Y; Oxadiazoles; Piperazines; Receptors, Serotonin; GR 127935; sibutramine;

Mesh terms: Animals; Appetite Depressants/pharmacology; Cyclobutanes/pharmacology; Dose-Response Relationship, Drug; Eating/drug effects; Male; Neuropeptide Y/pharmacology; Oxadiazoles/pharmacology; Piperazines/pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Serotonin/classification;

Citations: - Central GABA receptor agonists: comparison of muscimol and baclofen.

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