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Decreased social, drug, and food reward sensitivity in adolescent mice

Misiolek, K.; Chroszcz, M.; Klimczak, M.; Rzeszut, A.; Netczuk, J.; Ziolkowska, B.; Szumiec, L.; Kaczmarczyk-Jarosz, M.; Harda, Z.; Rodriguez Parkitna, J.

2025-08-22 animal behavior and cognition
10.1101/2025.08.18.670792 bioRxiv
Show abstract

Adolescence shapes adaptive adult behaviors. Most studies compare single adolescent and adult age groups using only one type of reward, limiting insight into developmental trajectories underlying behavioral change. Here, we investigated how social, cocaine, and palatable food rewards become associated with environmental contexts in female and male C57BL/6 mice across early- (pubertal onset), mid- (peripubertal phase), and late- (sexual maturity) adolescence, compared to adults. Using the conditioned place preference (CPP) task, we found that generally all rewards induced place preference for the reward-associated context, with only minor effects of sex. In contrast, age significantly influenced CPP expression. Adolescent mice exhibited a significantly reduced CPP compared to adults in palatable food and social CPP paradigms, evident in both decreased mean conditioned context preference and lower proportion of animals that developed a preference after conditioning. Cocaine CPP was not significantly affected by age. Direct comparisons across CPP task outcomes further confirmed that age, rather than reward type or sex, was the primary factor influencing the magnitude of CPP. Specifically, mid- and late-adolescent mice showed reduced mean reward CPP, and mid-adolescents were less likely to express a reward preference relative to adults. Based on the behavioral analyses, we conclude that the lower expression of preference for a conditioned context in adolescent animals is due to developmental changes in reward sensitivity, rather than deficits in learning or higher novelty-seeking behavior.

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