Changes in food reward following smoking cessation: a pharmacogenetic investigation

Rationale: Despite the high prevalence and public health significance of weight gain following smoking cessation, little is known about the underlying bio-behavioral mechanisms or effective therapies. Objectives: We evaluated the effects of bupropion on food reward following smoking abstinence and the moderating influence of genotype. Methods: Seventy-one smokers of European ancestry were genotyped for the dopamine D2 receptor (DRD2) Taq1 polymorphism and randomized to treatment with bupropion (300 mg) or placebo for smoking cessation. Subjects participated in two behavioral laboratory sessions during which the rewarding value of food was assessed using a behavioral economics measure: session 1 occurred prior to medication and before cessation of smoking; session 2 occurred following 3 weeks of medication and 1 week of sustained abstinence. Results: Carriers of the DRD2 A1 minor allele exhibited significant increases in the rewarding value of food following abstinence from smoking, and these effects were attenuated by bupropion treatment (P=0.03 for medication by genotype interaction). Further, higher levels of food reward at session 2 (post-quit) predicted a significant increase in weight by 6-month follow-up in the placebo group, but not in the bupropion-treated group (P=0.006 for medication by food reward interaction). Conclusions: These results provide new evidence that the increase in body weight that occurs following smoking cessation is related to increases in food reward, and that food reward is partly determined by genetic factors. Bupropion's efficacy in attenuating abstinence-induced weight gain may be attributable, in part to decreasing food reward.