Animal studies demonstrate that peripubertal social stress markedly increases the risk for subsequent substance use in adulthood. However, whether non‐social stress has a similar long‐term impact is not clear, and whether male and female animals show different sensitivity to peripubertal non‐social stress has not been examined. In the present study, we addressed these issues by introducing two non‐social stressors (elevated platform and predator odor 2,5‐Dihydro‐2,4,5‐trimethylthiazoline) to male and female Wistar rats during adolescence (postnatal days 28–30, 34, 36, 40, and 42), then tested reward‐related behaviors during adulthood, including morphine‐induced conditioned place preference (CPP, 1 mg/kg morphine or 5 mg/kg morphine) and hyperlocomotor activity (5 mg/kg morphine). We found that adult male rats, but not females who were exposed to peripubertal non‐social stressors showed enhanced morphine‐induced CPP. Moreover, morphine‐induced increase in locomotor activity was also significantly increased in adult male rats, but not in females. These results indicate that peripubertal exposure to repeated non‐social stress may enhance sensitivity to the rewarding effects of opioids in adulthood in a sex‐dependent manner, with males being even more sensitive than females in this regard.

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