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Genetic and depressive traits moderate the reward-enhancing effects of acute nicotine in young light smokers.

Rates of light smoking have increased in recent years and are associated with adverse health outcomes. Reducing light smoking is a challenge because it is unclear why some but not others, progress to heavier smoking. Nicotine has profound effects on brain reward systems and individual differences in nicotine's reward-enhancing effects may drive variability in smoking trajectories. Therefore, we examined whether a genetic risk factor and personality traits known to moderate reward processing, also moderate the reward-enhancing effects of nicotine. Light smokers (n=116) performed a Probabilistic Reward Task to assess reward responsiveness after receiving either nicotine or placebo (order counterbalanced). Individuals were classified as nicotine dependence 'risk' allele carriers (rs16969968 A-allele carriers) or non-carriers (non-A-allele carriers), and self-reported negative affective traits were also measured. Across the whole sample, reward responsiveness was greater following nicotine compared to placebo (p=0.045). For Caucasian A-allele carriers but not non-A-allele carriers, nicotine enhanced reward responsiveness compared to placebo for those who received the placebo first (p=0.010). Furthermore, for A-allele carriers but not non-A-allele carriers who received nicotine first, the enhanced reward responsiveness in the nicotine condition carried over to the placebo condition (p<0.001). Depressive traits also moderated the reward-enhancing effects of nicotine (p=0.010) and were associated with more blunted reward responsiveness following placebo but enhanced reward responsiveness following nicotine. These findings suggest that individual differences in a genetic risk factor and depressive traits alter nicotine's effect on reward responsiveness in light smokers and may be important factors underpinning variability in smoking trajectories in this growing population.