Acute behavioural effects of bupropion and naltrexone, alone and in combination, in non-deprived male rats presented with palatable mash

Abstract

In appetite research, drugs frequently progress to clinical trials on the basis of outcome (reduced food intake/body weight gain) with insufficient attention to process (behavioural analysis). Although bupropion and naltrexone (alone and in combination) reduce food consumption in rodents and humans, their effects on behaviour during feeding tests have not been thoroughly investigated. This study aimed to assess the behavioural specificity of anorectic responses to bupropion, naltrexone and their combination. Video analysis was employed to characterise the behavioural effects of acute systemic treatment with bupropion (10.0-40.0 mg/kg), naltrexone (0.1-3.0 mg/kg) and combined bupropion (20 mg/kg) plus naltrexone (0.1-1.0 mg/kg) in non-deprived male rats exposed for 1 h to palatable mash. Particular attention was paid to the behavioural satiety sequence (BSS). In experiment 1, the anorectic response to 40 mg/kg bupropion was associated with significant psychomotor stimulation and a complete disruption of the BSS. In experiment 2, the anorectic response to 3 mg/kg naltrexone was associated with an accelerated but otherwise normal BSS. In experiment 3, the co-administration of 20 mg/kg bupropion and naltrexone (0.1 and 1.0 mg/kg) not only produced an additive anorectic profile (including a reduced rate of eating), but the addition of the opioid receptor antagonist also concurrently attenuated the psychomotor stimulant response to the atypical antidepressant. Low-dose co-treatment with naltrexone and bupropion produces a stronger suppression of appetite than that seen with either agent alone and has the additional advantage of reducing some of the unwanted effects of bupropion.