Rationale: The clinical success of the antidepressant bupropion, marketed as Zyban in smoking cessation, presents an ideal opportunity to unravel its mechanism of action utilising animal models of nicotine dependence.
Objective: The present experiments utilise bupropion as a reference compound to examine putative interactions with stimulus properties of nicotine in rats.
Methods and results: In male hooded Lister rats, bupropion (10 and 30 mg/kg IP) administered 30 min prior to each intravenous nicotine (0.03 mg/kg per infusion) self-administration session failed to attenuate rates of nicotine intake. Moreover, following the large dose of bupropion, nicotine intake was enhanced and response rates remained elevated throughout the 28-day course of treatment. To examine interactions with subjective effects of nicotine, rats trained to discriminate nicotine (0.2 mg/kg SC) from vehicle were tested with bupropion (1, 3, 10 and 30 mg/kg IP). Bupropion pre-treatment failed to exert a "nicotine-like" action and also failed to attenuate the orderly dose-related discrimination function of nicotine (0.05-0.4 mg/kg SC) in rats. Using the conditioned taste aversion procedure to assess the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake, bupropion (3, 10 and 30 mg/kg IP) pre-treatment failed to modify the aversive effects produced by a threshold dose of nicotine (0.2 mg/kg SC).
Conclusions: The results obtained with bupropion in these animal models of dependence suggest this antidepressant may not directly interact with stimulus properties of nicotine; rather its clinical efficacy may be exposed in animal models that are based upon chronic exposure to nicotine and upon abstinence effects.