A Method for Psychosocial Stress-Induced Reinstatement of Cocaine Seeking in Rats.

We describe a novel preclinical model of stress-induced relapse to cocaine use in rats using social defeat stress, an ethologically valid psychosocial stressor in rodents that closely resembles stressors that promote craving and relapse in humans. Rats self-administered cocaine for 20 days. On days 11, 14, 17, and 20, animals were subjected to social defeat stress or a nonstressful control condition following the session, with discrete environmental stimuli signaling the impending event. After extinction training, reinstatement was assessed following re-exposure to these discrete cues. Animals re-exposed to psychosocial stress-predictive cues exhibited increased serum corticosterone and significantly greater reinstatement of cocaine seeking than the control group, and active coping behaviors during social defeat episodes were associated with subsequent reinstatement magnitude. These studies are the first to describe an operant model of psychosocial stress-induced relapse in rodents and lay the foundation for future work investigating its neurobiological underpinnings.