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

Abstract

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.

Figure 1

Effect of various doses of sibutramine on food intake of 24 h food-deprived rats. Sibutramine (1–10 mg kg⁻¹) was dissolved in distilled water and given p.o. 60 min before the test. Food intake corrected for spillage was measured for 1 h and expressed as g 100 g⁻¹ of body weight. Values are the mean±s.e.mean of ten animals per group. ^*=P<0.05 ^**=P<0.001 vs controls. Dunnett's test.

Figure 2

Effect of various doses of sibutramine on eating caused by NPY injected into the PVN. Sibutramine (3–10 mg kg⁻¹) was dissolved in distilled water and given p.o. 60 min before the test. NPY (235 pmol 0.5 μl⁻¹) was injected into the PVN immediately before the test. Food intake corrected for spillage was measured for 1 h and expressed as g 100 g⁻¹ of body weight. Values are the mean±s.e.mean of ten animals per group. ^**=P<0.01 vs controls. Dunnett's test.

Figure 3

Effect of GR127935 on the reduction in food intake caused by sibutramine in NPY injected rats. Sibutramine (6.0 mg kg⁻¹ p.o.) and GR127935 (1.0 mg kg⁻¹ s.c.) were dissolved in distilled water and given 60 min and 90 min before the test. NPY (235 pmol 0.5 μl⁻¹) was dissolved in distilled water and injected into the PVN immediately before the test. Values are the mean±s.e.mean of at least five animals per group. ^**=P<0.01 vs vehicle treated rats. Tukey's test. Fint(1.24)=0.0; P>0.05; Two-Way-ANOVA.