Peripubertal stress of male, but not female rats increases morphine-induced conditioned place preference and locomotion in adulthood.

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.