A distinct adolescent profile for activity and dopamine release in the nucleus accumbens during Pavlovian conditioning

Abstract

Across species, adolescence is a time of heightened reward sensitivity and enhanced impulsivity and risk-taking. In adults, these behavioral features are linked with a tendency to approach and interact with reward-associated cues - a behavior known as sign tracking - which is thought to reflect the transfer of incentive salience from reward to cue. Counterintuitively, adolescents are less likely to exhibit sign tracking, compared with adults, and more likely to exhibit goal tracking, or approach to the site of reward. To investigate a possible neural basis for this age difference, we recorded the activity of individual neurons in the nucleus accumbens (NAc) of male and female rats during Pavlovian conditioning in adolescence and adulthood. In a separate group, we used a fluorescent indicator (GRABDA) to measure dopamine release at the same ages. We found that cue-evoked NAc activity increased over the course of training in adolescents and then further in adulthood. The majority of adolescents were goal trackers or intermediates, for whom reward-evoked activity peaked during adolescence and declines in adulthood, correlating with increased prevalence and intensity of sign tracking. Meanwhile, cue-evoked dopamine release was markedly higher in sign trackers than in goal trackers at all time points. These results suggest that the progression from adolescence to adulthood may be accompanied by changes in the engagement of the mesolimbic dopamine system and/or the responsivity of NAc neural signaling to dopamine, contributing to limited sensitivity to reward cues, coupled with heightened sensitivity to primary rewards, in adolescent animals. Significance StatementAdolescence is a time of enhanced reward sensitivity, impulsivity, and risk-taking, making adolescents vulnerable to drug use and other risky behaviors. In adults, attraction to reward-associated cues - which can be modeled in animals using a behavior called sign tracking - plays an important role in risky behaviors. Surprisingly, we find that adolescents exhibit less sign tracking compared with adults. Here, we investigate the neural circuits underlying this age difference by monitoring neural activity and dopamine release in the nucleus accumbens (NAc), a key brain area for reward-seeking behavior, in the same animals as adolescents and as adults. We find that the majority of adolescents show a reduced neural sensitivity to reward cues, but a heightened neural response to the reward itself.