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

Abstract

1. 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. 2. 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). 3. 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-HT(2A/2C), 0.5 and 1.0 mg kg-1) and GR127935 (5-HT(1B/1D), 0.5 and 1.0 mg kg-1) did not modify the hypophagic effect of sibutramine, while SB206553 (5-HT(2B/2C), 5 and 10 mg kg-1) slightly but significantly reduced it (Fint(2.53)= 3.4; P < 0.05). 4. 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). 5. The results suggest that, with the possible exception of a partial involvement of 5-HT(2B/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.