Effects of chronic social defeat stress on social behavior and cognitive flexibility for early and late adolescent

This study investigated the risk to social behavior and cognitive flexibility induced by chronic social defeat stress (CSDS) during early and late adolescence (EA and LA). Utilizing the “resident-intruder” stress paradigm, adolescent male Sprague-Dawley rats were exposed to CSDS during either EA (postnatal days 29–38) or LA (postnatal days 39–48) to explore how social defeat at different stages of adolescence affects behavioral and cognitive symptoms commonly associated with psychiatric disorders. After stress exposure, the rats were assessed for anxiety-like behavior in the elevated plus maze, social interaction, and cognitive flexibility through set-shifting and reversal-learning tasks under immediate and delayed reward conditions. The results showed that CSDS during EA, but not LA, led to impaired cognitive flexibility in adulthood, as evidenced by increased perseverative and regressive errors in the set-shifting and reversal-learning tasks, particularly under the delayed reward condition. This suggests that the timing of stress exposure during development has a significant impact on the long-term consequences for behavioral and cognitive function. The findings highlight the vulnerability of the prefrontal cortex, which undergoes critical maturation during early adolescence, to the effects of social stress. Overall, this study demonstrates that the timing of social stressors during adolescence can differentially shape the developmental trajectory of cognitive flexibility, with important implications for understanding the link between childhood/adolescent adversity and the emergence of psychiatric disorders.