Role of nicotinic acetylcholine receptors in the effects of cocaine-paired contextual stimuli on impulsive decision making in rats

Abstract

Chronic cocaine exposure produces unconditioned enhancement in impulsive decision making; however, little is known about the effects of cocaine-paired conditioned stimuli on this behavior. Thus, this study explored the effects of cocaine-paired contextual stimuli on impulsive decision making and the contribution of nicotinic acetylcholine receptors (nAChRs) to this phenomenon. Rats were trained to achieve stable performance on a delay discounting task, which involved lever press-based choice between a single food pellet (small reward) available immediately and three food pellets (large reward) available after a 10-, 20-, 40-, or 60-s time delay. Rats then received Pavlovian context-cocaine (15 mg/kg, i.p.) and context-saline (1 ml/kg, i.p.) pairings in two other, distinct contexts. Subsequently, delay discounting task performance was assessed in the previously cocaine-paired or saline-paired context following pretreatment with saline or cocaine (15 mg/kg, Experiment 1) or with saline or the nAChR antagonist, mecamylamine (0.2 and 2 mg/kg, Experiment 2), using counterbalanced within-subjects testing designs. Independent of cocaine pretreatment, rats exhibited greater decrease in preference for the large reward as a function of delay duration in the cocaine-paired context, relative to the saline-paired context. Furthermore, systemic mecamylamine pretreatment dose-dependently attenuated the decrease in preference for the large reward in the cocaine-paired context, but not in the saline-paired context, as compared to saline. Cocaine-paired contextual stimuli evoke a state of impulsive decision making, which requires nAChR stimulation. Drug context-induced impulsivity likely increases the propensity for drug relapse in cocaine users, making the nAChR an interesting target for drug relapse prevention.