Cocaine addiction is a chronic relapsing disorder with devastating psychosocial, health and societal consequences. Emerging data clearly indicate the importance of studying sex-specific effects in cocaine dependence - a growing problem for women in this country. Stress has been identified as one of the key factors in increasing the vulnerability to develop cocaine dependence in women. Women also report stress and negative mood as playing a pivotal role in the continued drug use and relapse cycle. While there have been attempts to understand the mechanisms underlying the association between stress and cocaine addiction, systematic research on sex-specific factors that contribute to this association has been rare. The goal of this Center is to use interdisciplinary approaches of examination: (A) to assess the effects of early life stress, sex hormones and stress hormones on cocaine reinforcement and the risk of developing cocaine dependence; and (B) to understand the contribution of sex-based factors in the association between stress and cocaine relapse. These goals will be achieved using multidisciplinary laboratory and clinical research conducted in animals and in humans. A greater understanding of the interactions between sex, stress and cocaine dependence will be significant in the development of sex-specific prevention and treatment approaches that will specifically affect the health of women with cocaine dependence. The following specific aims will be achieved by the SCOR: (1) To establish a collaborative multidisciplinary research Center that will address the study of sex-specific factors in the relationship between stress and cocaine addiction. (2) To conduct a series of programmatic animal and human research studies aimed at understanding sex-specific factors in the relationship between stress and cocaine addiction. (3) To develop a collaborative research program that will utilize SCOR core resources to facilitate the investigation of sex-specific factors in ongoing independently-funded research at Yale relating to the etiology, neurobiology and treatment of cocaine addiction. (4) To assist a range of young investigators from different disciplines in conducting sex-specific research on stress and cocaine addiction through mentorship activities of Center staff.