Examination of the effects of varenicline, bupropion, lorcaserin, or naltrexone on responding for conditioned reinforcement in nicotine-exposed rats.

Smoking tobacco remains one of the leading causes of preventable deaths in North America. Nicotine reinforces smoking behavior, in part, by enhancing the reinforcing properties of reward-related stimuli, or conditioned stimuli (CSs), associated with tobacco intake. To investigate how pharmaceutical interventions may affect this property of nicotine, we examined the effect of four US Food and Drug Administration (FDA) approved drugs on the ability of nicotine to enhance operant responding for a CS as a conditioned reinforcer. Thirsty rats were exposed to 13 Pavlovian sessions where a CS was paired with water delivery. Nicotine (0.4 mg/kg) injections were administered before each Pavlovian session. Then, in separate groups of rats, the effects of varenicline (1 mg/kg), bupropion (10 and 30 mg/kg), lorcaserin (0.6 mg/kg), and naltrexone (2 mg/kg), and their interaction with nicotine on responding for conditioned reinforcement were examined. Varenicline and lorcaserin each reduced nicotine-enhanced responding for conditioned reinforcement, whereas naltrexone had a modest effect of reducing response enhancements by nicotine. In contrast, bupropion enhanced the effect of nicotine on this measure. The results of these studies may inform how pharmaceutical interventions can affect smoking cessation attempts and relapse through diverse mechanisms, either substituting for, or interacting with, the reinforcement-enhancing properties of nicotine.