Exploring behavioral and molecular mechanisms of nicotine reward in adolescent mice

Abstract

Tobacco smoking during adolescence has become a prominent preventable health problem faced in the United States. Addictive properties of smoking are thought to have a pronounced effect at a young age, thereby increasing vulnerability to a life-long addiction and decreasing the likelihood of smoking cessation during adulthood. Learning and memory involvement in nicotine reward was assessed in early adolescent (PND 28-34) and adult (PND 70+) male ICR mice by conducting conditioning sessions of nicotine (0.5mg/kg) acquisition at varying time-spans, and evaluating extinction and reinstatement of nicotine preference using Conditioned Place Preference. Acquisition studies resulted in a significant preference for nicotine after 3 days of conditioning for both age groups, but not after only 1 or 2 conditioning days. In the extinction study, adolescent mice exhibited preference for nicotine 72 h after the last conditioning session, whereas preference for nicotine was extinct in adult mice by 72 h. Reinstatement studies showed adolescent mice, but not adult mice, recovering nicotine preference after a priming injection of 0.1mg/kg nicotine on day 9 after the mice underwent extinction. No significant differences were found when nAChRs were quantified in both early adolescent and adult mice using binding techniques including cytisine sensitive, α-conotoxin-MII sensitive, and α-bungarotoxin sensitive nAChRs. Levels of striatal dopamine release were measured in both age groups using a dopamine release assay over a range of nicotine doses, which also resulted in no significant differences. More sensitive assays may facilitate in understanding the mechanisms of nicotine reward in adolescent mice.