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

Abstract

Background 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. Objective We investigated the role of social experience and social defeat stress during adolescence on social behavior and cocaine self administration (CocSelfAd) in early adulthood. Methods 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), intra-jugular catheters were implanted and CocSelfAd was analyzed. Results 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-hour continuous access binge compared to PH controls and SH defeated rats. Conclusions 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.

Adolescent Social Stress Produces an Enduring Activation of the Rat Locus Coeruleus and Alters its Coherence with the Prefrontal Cortex

“…Adult male rats repeatedly exposed to resident-intruder stress display endocrine, autonomic and behavioral features that characterize mood disorders in humans, underscoring the potential of this model to produce correlates of stress-related psychiatric diseases Rygula et al, 2005;Wood et al, 2010Wood et al, , 2012Wood et al, , 2013. Although less well studied, adolescent male rats exposed to repeated resident-intruder stress have been reported to have cognitive impairments and escalated cocaine self-administration when tested in adulthood (Burke and Miczek, 2015;Novick et al, 2013;Snyder et al, 2015).…”

A novel adolescent chronic social defeat model: reverse-Resident-Intruder Paradigm (rRIP) in male rats

“…Behavioral catalysts, such as food-deprivation and social isolation, conventionally used to enhance the aggressive disposition and territoriality of LE-Residents failed to facilitate these behaviors in the present study. While the exact mechanism for the role reversal was not investigated, previous studies with adolescent and adult LE rats highlight the use of screening methodology to select candidate animals exhibiting heightened levels of aggression (Burke & Miczek, 2015; Buwalda et al, 2011; Patki et al, 2015). In addition, our LE-Residents were not co-housed or pre-exposed to dominant-subordinate social interaction prior to CSDS.…”

“…This enhanced aggression may develop from increases in social exploration and reductions in fear/anxiety behavior following single-housing during adolescence. For example, Burke and Miczek (2015) reported single-housed SD adolescent rats spent more time “approaching, following and crawling under an adult LE-Resident”. This led to more attacks and bites from the resident, but surprisingly less freezing behavior from the SD-Intruder (Burke & Miczek, 2015).…”

“…For example, Burke and Miczek (2015) reported single-housed SD adolescent rats spent more time “approaching, following and crawling under an adult LE-Resident”. This led to more attacks and bites from the resident, but surprisingly less freezing behavior from the SD-Intruder (Burke & Miczek, 2015). These observations and ours are consistent with increases in novelty-seeking and risk-taking behaviors (i.e.…”

“…While there is a rich animal literature on the effects of adolescent SDS on the adult brain and behavior, few studies have addressed how SDS affects the adolescent animal (Burke & Miczek, 2015, Burke et al, 2016; Buwalda et al, 2011). Adolescence is a transitional period, where reliance on parental guidance fades into independence as an adult.…”