Characterization of the effects of bupropion on the reinforcing properties of nicotine and food in rats.

Bupropion is an atypical antidepressant drug that is the only nonnicotine-based prescription medicine approved for smoking cessation by the Food and Drug Administration. The aim of the present experiments was to investigate the effects of bupropion (5-40 mg/kg) on the reinforcing properties of nicotine and food in rats. The effects of bupropion were studied under two schedules of reinforcement: a fixed ratio 5 time-out 20-sec (FR5 TO20 s) and a progressive ratio (PR). Rats were trained to respond for nicotine (0.01 or 0.03 mg/kg/infusion, free base) or food under the FR5 TO20 s schedule. Pretreatment with the highest dose of bupropion (40 mg/kg) resulted in a significant reduction (approximately 50%) of nicotine intake in rats self-administering 0.03 mg/kg/infusion of nicotine. The same dose of bupropion also decreased (approximately 40%) the self-administration of 0.01 mg/kg/infusion of nicotine, but this effect did not reach statistical significance. Pretreatment with bupropion slightly (approximately 15%) reduced responding for food under the FR5 TO20 s schedule. Finally, pretreatment with bupropion did not affect the self-administration of nicotine (0.03 mg/kg/infusion) under a PR schedule, but dose-dependently increased responding for food under the same PR schedule. These findings indicate that a high dose of bupropion decreases the reinforcing properties of nicotine as measured under an FR schedule, while having no apparent effects on breaking points for nicotine under a PR schedule that reflects both the reinforcing properties and the motivation to obtain nicotine. Copyright 2003 Wiley-Liss, Inc.