Escalation of cocaine self-administration in adulthood after social defeat of adolescent rats: role of social experience and adaptive coping behavior

The link between adolescent social stress and substance abuse is modeled in social defeat of adolescent male rats, at an age when social experiences are essential for neurobehavioral maturation. We investigated the role of social experience and social defeat stress during adolescence on social behavior and cocaine self-administration (CocSelfAd) in early adulthood. We manipulated social experience by housing male rats in pairs (PH) or singly (SH) on postnatal day (P) 21. In addition, rats were subjected to social defeat from P35-44. Social behavior was measured during the first and last social defeat in PH and SH adolescents and PH adults. After assessing the behavioral response to novelty and cocaine (P57-61), intrajugular catheters were implanted and CocSelfAd was analyzed. Residents were less aggressive toward PH adolescent intruders compared to PH adult intruders. Adults were submissive and defensive when attacked, whereas PH adolescents froze. In the course of repeated defeats, adolescent PH rats increased freezing, while SH rats decreased freezing. Longer attack-induced freezing after repeated defeats predicted escalated CocSelfAd in adulthood. PH controls acquired CocSelfAd more slowly than PH defeated and SH rats. Defeated PH rats increased CocSelfAd during progressive ratio schedules of reinforcement and during a 24-h continuous access binge compared to PH controls and SH defeated rats. Social defeat in adolescence of PH rats caused persistent increases in adult CocSelfAd. Adolescent PH rats coped with attacks adaptively by increasing freezing behavior after repeated social defeats, a measure that predicted CocSelfAd in adulthood.