Dysregulation of reward responsiveness during nicotine withdrawal and nicotine re-exposure in rats using a translational task

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Abstinence from smoking is associated with depression-like symptoms, including deficits in reward processing, which are hypothesized to play an important role in relapse. Reward responsiveness (i.e., the ability to modulate behavior as a function of reinforcement history) is disrupted in major depressive disorder. We determined whether reward responsiveness was affected during nicotine withdrawal and subsequent nicotine re-exposure in male Wistar rats using a novel behavioral task that was recently developed to be analogous to an objective clinical assessment of reward responsiveness. Withdrawal from chronic nicotine (6.32 mg/kg/day, base; sc; 28 days; n=19), but not saline (n=20), administration diminished reward responsiveness. Two to eight weeks after termination of chronic nicotine, acute nicotine administration (0, 0.125, 0.25, 0.5 mg/kg, base; sc; administered in a Latin-square design) dose-dependently increased reward responsiveness. Conversely, acute nicotine administration in previously salinetreated rats dose-dependently decreased reward responsiveness. These results suggest that chronic nicotine exposure induces a long-lasting dysregulation of the processing of natural rewards. The disruption of reward responsiveness during immediate withdrawal may contribute to the depression-like state associated with withdrawal, while the nicotine-induced enhancement of reward responsiveness after withdrawal may contribute to relapse to tobacco smoking in order to re-instate responsiveness to natural rewards. Thus, treatment of deficits in reward responsiveness in abstinent smokers may facilitate smoking cessation.

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