Behaviour of female mice defeated in an inter-female aggression protocol predicts resilience to cocaine-induced conditioned place preference

Several studies have demonstrated that exposure to different protocols of social defeat induces anxiety- and depression-like symptoms in male and female mice. Moreover, male mice exposed to an intermittent social defeat (ISD) show increased vulnerability to the rewarding effects of cocaine, although several behavioural traits have been found to confer resilience against this effect. However, the effects of ISD on the vulnerability to drugs of abuse in female mice have not been studied. Thus, our aim was to evaluate the short-term behavioural effects of ISD and its long-term influence on the rewarding effects of cocaine in female mice. Intruder female mice were exposed to an ISD protocol and performed the elevated plus maze, hole-board, social interaction, splash, object recognition and tail suspension tests 24 or 48 h after the last episode of defeat. Three weeks later, female mice underwent the conditioned place preference procedure with cocaine. ISD exposure induced a slight anxiogenic effect, decreased novelty-seeking behaviour and enhanced sensitivity to the conditioned rewarding effects of cocaine. However, defeated female mice characterized by an active coping response during episodes of defeat and an avoidance of potential dangers in unknown environments did not develop cocaine preference. Our results show that defeat in an inter-female aggression protocol is a useful way to study the long-term consequences of social stress on cocaine reward and the behavioural traits associated with resilience.