Sibutramine-induced anorexia: Potent, dose-dependent and behaviourally-selective profile in male rats

The serotonin and noradrenaline reuptake inhibitor sibutramine has been licensed as an anti-obesity treatment for more than a decade. However, while inhibitory effects on food intake and weight gain are well documented, surprisingly little published detail exists regarding its influence on feeding and related behaviours. The present study was therefore designed to assess the effects of acute sibutramine treatment on food intake, the behavioural satiety sequence (BSS) and post-treatment weight gain. Subjects were 10 non-deprived adult male Lister hooded rats, tested with 0.5-3.0 mg/kg sibutramine hydrochloride during 1-h DVD-recorded test sessions with palatable mash. Our results show that sibutramine dose-dependently reduced food intake, an effect significant at all doses tested. Ethological analysis revealed very few behavioural effects, except for a dose-dependent reduction in time spent feeding and an increase in the frequency of resting. Behavioural specificity was further supported by time-bin analysis which confirmed both the structural integrity and dose-dependent acceleration of the BSS. Single dosing with sibutramine (3.0 mg/kg) also suppressed daily weight gain over the 24-72 h period post-dosing. Current data support the conclusion that the acute anorectic and weight loss efficacy of sibutramine in adult male rats is not secondary to behavioural disruption but, instead, is due largely to an acceleration in behavioural satiety. (C) 2008 Elsevier B.V. All rights reserved.