Repeated nicotine exposure during adolescence alters reward-related learning in male and female rats

Rationale: Repeated nicotine exposure causes neuroadaptations in limbic cortico-striatal circuits involved in learning and motivation. Such alterations are relevant to addiction because they are suggested to mediate the ability of smoking-associated stimuli to control behavior and to enhance nicotine-seeking and -taking behaviors. Female smokers report higher cue reactivity relative to their male counter parts, yet little is known about putative gender-specific effects of adolescent nicotine exposure on reward-related learning. Prior repeated nicotine exposure in adult male rats enhances Pavlovian approach behavior and conditioned reinforcement.

Objective: Given that smoking is typically initiated during adolescence, here we assessed the extent to which adolescent nicotine exposure impacts Pavlovian approach and conditioned reinforcement in male and female rats.

Methods: Rats were injected with nicotine on postnatal days 31-45 prior to training on Pavlovian approach behavior starting on day 51. They were trained to associate a conditioned stimulus (CS), illumination of a magazine light, and tone, with an unconditioned stimulus (US), the delivery of water, for 10-daily sessions, and then were tested on the acquisition of responding with conditioned reinforcement.

Results: Adolescent nicotine exposure selectively increased approach to the magazine during the CS in males but decreased approach to the magazine during the CS in female rats. Vehicle-exposed female rats, however, showed greater magazine approach during the CS than did male control rats. Prior nicotine exposure also enhanced conditioned reinforcement in both male and female rats.

Conclusions: Repeated exposure to nicotine during adolescence had opposite effects on Pavlovian approach behavior in male and female rats but enhanced acquisition of a new response with conditioned reinforcement. Novel information on how nicotine exposure influences reward-related learning during adolescence may increase our understanding of neurobiological mechanisms involved in the initiation of smoking behavior.