Behavioral and neuroimmune characterization of resilience to social stress: Rewarding effects of cocaine.

Preclinical studies have shown that social stress increases vulnerability to the reinforcing effects of cocaine. However, the results are not always homogeneous, revealing a subpopulation that does not show a preference for cocaine. Thus, the main aim of the present study was to characterize the behavioral profile of resilient mice to the stress-induced rewarding effects of cocaine using an animal model of repeated social defeat stress (SD). To this end, male adult mice of the C57/BL6 strain were exposed to SD and, three weeks later, assessed using the Conditioned Place Preference paradigm induced by an ineffective dose of cocaine (1mg/kg). Afterwards, the striatal levels of interleukin 6 were measured, as social stress usually induces a neuroinflammatory response. Control mice did not develop CPP, while defeated mice did overall develop a preference for the drug-paired compartment. Based on the conditioning score that they exhibited, the SD sample was subdivided into resilient (did not develop preference) and susceptible mice (developed preference). During the SD sessions, resilient animals showed less flight and submission behaviors than susceptible mice and they presented attack behaviors towards the residents, thereby showing their resistance to being defeated. There were no differences in the neuroinflammatory response, probably due to the long time elapsed after the last SD session. These results suggest that an active coping style to social stress may be decisive in protecting the individual from developing an addiction.