Chronic bupropion differentially alters the reinforcing, reward-enhancing and conditioned motivational properties of nicotine in rats

Bupropion is an effective anti-smoking agent in humans, but the behavioral mechanisms mediating this effect are unclear. The present studies assessed the effects of chronic bupropion on the reinforcing and reward-enhancing effects of self-administered nicotine, and on the motivational properties of a nicotine-associated conditioned reinforcer. The present studies also assessed the reward-enhancing effects of nicotine self-administration under different levels of access to nicotine, and the effects of enforced abstinence from self-administered nicotine on brain reward function and somatic signs. Rats were prepared with bipolar electrodes in the lateral hypothalamus and trained on a discrete trial intracranial self-stimulation (ICSS) task. After establishing stable ICSS thresholds, rats were prepared with intravenous catheters and allowed to self-administer nicotine at different levels of access. Self-administered nicotine lowered ICSS thresholds, thereby providing a measure of the reward-enhancing effects of nicotine. Abstinence from 6h/d 7d/wk nicotine self-administration was associated with increased somatic signs of nicotine withdrawal and unchanged brain reward thresholds. Chronic bupropion administration via subcutaneous osmotic minipump had no effect on nicotine self-administration, but attenuated nicotine-induced enhancement of brain reward function and enhanced the motivational properties of a previously nicotine-associated conditioned stimulus. Thus, it is unlikely that chronic bupropion exerts anti-smoking effects by attenuating the primary or conditioned reinforcing effects of nicotine. Rather, preclinical investigations suggest that bupropion attenuates nicotine-induced enhancement of brain reward function and reverses the anhedonic, somatic, and neurochemical correlates of nicotine withdrawal.