Sex-dependent effects of chronic stress on punished cocaine self-administration and cue-induced relapse to cocaine seeking.

We tested the effects of chronic stress on cocaine relapse after drug-reinforced responding was suppressed by punishment, an animal model of human relapse after self-imposed abstinence due to the negative consequences of drug use. Male rats displayed greater resistance to punishment than females, but daily stress decreased this resistance. Only female rats with a history of chronic stress displayed increased responding for cocaine cues from abstinence Day 1 to Day 8. Thus, the effects of chronic stress on punished cocaine self-administration and cue-induced relapse are dependent on biological sex, and may have implications for more targeted treatments for cocaine addiction.