Bidirectional changes in reward responsiveness during nicotine withdrawal and acute nicotine administration assessed in the response bias probabilistic reward task in rats

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Aims: Deficits in reward processing are hypothesized to play an important role in relapse amongst abstinent smokers. The aim of the present study was to determine the effects of nicotine withdrawal and subsequent nicotine exposure on reward responsiveness in rats. Reward responsiveness (i.e., the propensity to modulate behavior as a function of prior reinforcement experience) was assessed using a translational behavioral task originally developed for humans and recently adapted for rats. Methods: Male Wistar rats (n=34) were trained to discriminate two tones varying in duration in operant boxes for food pellets. During test sessions, one tone (rich) was reinforced three times more frequently than the other tone. Rats were tested after 24 hr spontaneous withdrawal from either nicotine (6.32 mg/kg/day, base) or saline delivered for 28 days via subcutaneous osmotic minipumps. The effects of acute nicotine (0, 0.125, 0.25, 0.5 mg/kg, base, sc) were assessed in the same rats between 2 and 8 weeks after termination of chronic nicotine administration using a Latin-square design. Results: Saline-treated rats developed a response bias towards the rich stimulus, while response bias was significantly decreased during nicotine withdrawal, reflecting diminished reward responsiveness. Acute nicotine administration (0.25, 0.5 mg/kg) potentiated response bias in rats previously exposed to chronic nicotine compared to saline-treated rats, reflecting enhanced reward responsiveness by acute nicotine in rats with previous nicotine experience. Conclusions: Decreased reward responsiveness during nicotine withdrawal and the enhancement of reward responsiveness by acute nicotine in rats with chronic nicotine exposure and withdrawal could potentially play an important role in relapse in abstinent smokers. Thus, treatment of deficits in reward responsiveness in abstinent smokers may facilitate smoking cessation

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