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

1 The effect of the 5-hydroxytryptamine (5-HT) and noradrenaline (NA) reupt ake 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 modi fied 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 antagonist s. Metergoline (non-selective, 0.3 and 1.0 mg kg(-1)), ritanserin (5-HT2A/2 C, 0.5 and 1.0 mg kg(-1)) and GR127935 (5-HT1B/1D, 0.5 and 1.0 mg kg(-1)) d id 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). 4 The reduction in food intake caused by 6.0 mg kg(-1) sibutramine in NPY-i njected rats was not modified by GR127935 (1.0 mg kg(-1)). 5 The results suggest that, with the possible exception of a partial involv ement of 5-HT2B/2C receptors in sibutramine's hypophagia in food-deprived r ats, 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 injectio n.