A major challenge for treating cocaine addiction is the propensity for abstinent users to relapse. Two important triggers for relapse are cues associated with prior drug use and stressful life events. Stress is one of the most common triggers for relapse, but the underlying neuronal mechanisms are not fully understood. Human studies indicate that exposure to chronic adverse life events is associated with increased relapse vulnerability in abstinent cocaine addicts, indicating a need for animal models that explore interactions between chronic stress and drug withdrawal. Studies in my laboratory are focused on studying the effects of cocaine and chronic stress exposure on long-lasting changes in relapse vulnerability, with the ultimate goal of developing treatment strategies to help recovering addicts maintain abstinence. To do so we use the `incubation of cocaine craving' animal model, in which cue-induced cocaine seeking in rats progressively intensifies during the first month of withdrawal from extended-access drug self-administration. By combining behavioral and biochemical techniques, we will assess the synergistic effects of cocaine and stress exposure during withdrawal on cellular and behavioral measures and, using stress resilience models, identify strategies to reverse such effects. Together, these studies will ultimately bring us closer to developing effective pharmacotherapies to prevent relapse.