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.
British Journal of Pharmacology – Wiley
Published: Jul 1, 1999
Keywords: ; ; ; ; ;
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