Hedonic and cognitive responses to cigarette smoking: Role of genetic variation in the nicotinic acetylcholine receptor system

The primary targets for nicotine in the brain are nicotinic acetylcholine receptors (nAChRs). Genetic polymorphisms in this system are likely to contribute to the rewarding properties of nicotine and potentially underlie individual differences in diverse aspects of smoking behavior, including subjective responses. The primary objective of this study was to examine the role of allelic variation in genes encoding for nAChR subunits CHRNA3, CHRNA4, and CHRNA5 on acute responses to nicotine via cigarette smoking. In a human laboratory study, 64 smokers participated in an experimental session following 8-hours of nicotine abstinence. Hedonic and cognitive responses were measured during nicotine deprivation and nicotine satiety. Participants also completed self-reported measures of subjective responses after smoking each of three 1.0mg cigarettes. Compared with smokers with CHRNA3 CC the genotype, TT genotypes reported experiencing fewer positive affective effects of cigarette smoking. Physiological effects of smoking were more pronounced in CHRNA4 TC genotypes than in individuals with the TT genotype. Smokers with CHRNA5 AG genotypes reported less affective enhancement compared with GG genotypes. This study provides additional support for the role of variation in the nAChR system on individual differences in responses to cigarette smoking and provides new evidence for the role of the nAChR system on specific subjective effects that may maintain cigarette smoking behavior.