Cocaine use disorder is a chronic disease characterized by the loss of control over drug-seeking and taking. It has been shown that transition between social use and loss of control, is mainly observed in vulnerable users; such susceptibility depends on environmental and biological factors. Our group is focused on understanding the role of Social Isolation (SI), as an environmental factor, and sex as biological factor, in the vulnerability to cocaine exposure in rats. Recently, we showed that 5 days of SI from postnatal days 30 to 35 (PND30-35) increases the response to cocaine in adult male rats. Also, previous results showed different behavioral responses to isolation in male and female rats. In the present study, we evaluate if 5 days of SI (PDN30-35) would induce cocaine sensitization on PND45, in female and male rats. So far, our preliminary results show that cocaine (5mg/kg i.p.) induced a higher locomotor response in isolated female rats compared to non-isolated ones; while in males cocaine induced a similar response in both groups. However, more animals need to be run to draw a conclusion. Moreover, animal’s behavior during habituation will be analyzed. While future experiments will evaluate the levels of b-catenin in Prefrontal Cortex as a measured of Wnt pathway activity. Our working hypothesis is that SI increases cocaine vulnerability by decreasing the activity of Wnt canonical pathway in PFC in a sex dependent manner.