Cocaine abuse has increased during the last decade so that 2.4 million Americans currently use cocaine, and of those addicted 39.5 percent are female. Women begin using cocaine and enter treatment at earlier ages than men and have more severe cocaine use at treatment intake than men. In fact, from initial use to dependence female humans and rats progress at a faster rate than males and have greater motivation to obtain cocaine. Current treatments for all substance use disorders (and we lack any medication treatment for cocaine use disorders) do not mitigate stress-potentiated drug use. We have a very limited understanding of sex differences in response to stressors and their effect on drug self-administration, particularly in the context of medication and implications for treatment outcome. While stress augments drug intake and relapse, a positive social environment may serve to reduce drug use. The latter could act by reducing stress levels, and thereby decreasing drug intake. Preliminary data show that pair housing in laboratory rats reduced the motivation to take cocaine in females, but not in males. Oxytocin (OT) is a likely Candidate for bridging the gap between addiction and the protective effects of a social environment. We hypothesize that OT, in combination with social housing, will reduce the motivation to take cocaine. We will investigate whether exogenous OT can reduce the motivation to take cocaine and if this is influenced by the social housing conditions, focusing on females. Furthermore, we hypothesize that OT and pair housing exert their effects by modulating cocaine- induced dopamine release. Therefore, we will investigate if pair- housing and OT, or the combination of both, affect cocaine-induced dopamine release in the nucleus accumbens, comparing cocaine-naive and self-administration-experienced rats. The results from these studies will provide an indication if OT can be used as a therapeutic agent for the treatment of cocaine- addiction, and if the presence of social contacts will augment the effects of OT. PUBLIC HEALTH RELEVANCE: Effective treatments for cocaine addiction are limited, and appear to be more successful in men than women. Even though more men are addicted to cocaine, drug use in women is increasing, and the addictive effects of drugs of abuse are greater in women. This research is important for mental health as it will investigate the impact of social factors on the effects of drugs of abuse in females, and how this affects neural function. Insight into the protective properties of social support could ultimately lead to improved treatment options for cocaine addiction in both women and men.