ABSTRACT
RATIONALE: Bupropion reduces discomfort and craving associated with smoking cessation. This study determined whether a rat model of nicotine dependence could detect such nicotine abstinence-alleviating effects. OBJECTIVES: Experiments determined whether the abstinence-alleviating effects of bupropion were detectable by (1) behavioral abstinence signs precipitated by the nicotinic antagonist mecamylamine, (2) place aversion conditioned to mecamylamine-precipitated nicotine abstinence, and (3) spontaneous behavioral abstinence signs after abrupt nicotine withdrawal. METHODS: In experiments 1 and 2, nicotine-dependent rats were coinfused for 7 days with 3.15 mg/kg/day nicotine and 20 mg/kg/day bupropion or with nicotine alone. They were then challenged with 1 mg/kg mecamylamine and observed for behavioral abstinence signs (experiment 1) or place aversion conditioned to precipitated abstinence (experiment 2). In experiment 3, rats were nicotine-infused for 7 days as above. A day after termination of nicotine infusion, rats were observed for spontaneous nicotine abstinence signs before and after injection with saline or bupropion. RESULTS: In experiment 1, rats coinfused with nicotine and bupropion had significantly fewer mecamylamine-precipitated abstinence signs than rats infused with nicotine alone but similar numbers to rats infused with saline alone. In experiment 2, bupropion pretreatment significantly reduced the aversiveness of mecamylamine-precipitated nicotine abstinence. In experiment 3, a single bupropion injection dose-dependently alleviated spontaneous nicotine abstinence syndrome. CONCLUSIONS: These results suggest that these rat models of nicotine dependence and abstinence syndrome may be useful in detecting nicotine abstinence-alleviating effects of potential medications for smoking cessation. The effects of acute bupropion administration raise interesting questions regarding bupropion's mechanism of action.
