Effects of Adolescent Nicotine Exposure on Adult Cocaine Reward, Aversion and Self-Administration

Rationale. These studies examined adolescent nicotine pre-exposure on the rewarding and aversive effects of cocaine and the relationship of these changes to adult cocaine self-administration. Methods. In Experiment 1, male rats on postnatal day (PND) 28 were divided into two groups and given once daily 0.6 mg/kg injections of nicotine or vehicle (until PND 43). They were then allowed to age untreated to adulthood (PND 66), exposed to habituation and pretests (PND 67-77) and then tested for the aversive and rewarding effects of cocaine in a combined conditioned taste avoidance (CTA)/place preference (CPP) procedure (PND 78-90). Briefly, rats were placed in wire mesh hanging cages, given access to a novel saccharin solution, injected with cocaine (5.6, 10 or 18 mg/kg) or vehicle then placed in CPP chambers. In Experiment 2, rats were pre-exposed to nicotine as described above with the addition of baseline and locomotor (every third injection day) tests to examine nicotine-induced locomotor sensitization. They were then allowed to age untreated to adulthood (PND 76), implanted with jugular catheters and allowed to recover for at least 5 days. Beginning on PND 90, rats were tested for cocaine self-administration (0.25 or 0.75 mg/kg), progressive ratio (PR) responding, extinction and cue-induced reinstatement. Results. In Experiment 1, rats showed a significant CTA Trial x Drug interaction (p = .012) with cocaine groups consuming less saccharin over Trials, but no Pre-exposure or Dose group differences. For place preferences, there was no main effect of Pre-exposure or Dose or any interactions. Therefore, data were collapsed across Pre-exposure and Dose. There was a significant main effect of Drug (p=.008) such that the cocaine group spent more time on the drug paired side (DPS) than the vehicle group. In Experiment 2, the nicotine group showed sensitized locomotor activity over nicotine injections when compared to controls, showing that the nicotine was behaviorally active. All rats in Experiment 2 showed clear, dose-dependent responding during cocaine acquisition, PR, extinction and reinstatement with no effect of nicotine pre-exposure.Conclusions. These studies suggest that adolescent nicotine pre-exposure does not have an impact on adult cocaine self-administration or its affective properties, at least under these specific parametric conditions. Further research is needed to clarify the conditions under which adolescent nicotine induces changes in the adult affective properties and self-administration patterns of cocaine. A clearer understanding of these factors could lead to better drug abuse treatment and prevention strategies in the future.