? The goals for this 3-year Mentored Research Scientist Development Award (K01) application are to: (1) Re-establish an investigative career after the hiatus necessitated by attending to my wife's fatal illness; (2) Upgrade my research skills pertaining to methodology for researching the effects of acute stress on the liability to DSM-IV substance use disorders (SUD); and, (3) Devote full time effort to research without clinical or teaching duties, and limiting organizational duties to research conducted at the NIDA-funded Center for Education and Drug Abuse (CEDAR) which has been funded through April 2009. ? ? My research project will elucidate the role of acute stress reactivity in a cohort of young adults (N=160) age 22, in a modal period of maximum lifetime risk for developing SUD. Participants are recruited from an ongoing prospective investigation of SUD under the aegis of the NIDA-funded CEDAR and have already been studied in four prior waves of biobehavioral data collection conducted at ages 10-12, 12-14, 16 and 19. This project will delineate the conjoint impact of three putative SUD risk factors: (1) parental phenotype (parental SUD+/parental SUD-), (2) offspring's neurobehavior disinhibition (ND); and, 3) acute stress reactivity in controlled laboratory studies using physiological and psychological measurements. ? ? Through the education and training component I will acquire the expertise to document stress reactivity via hypothalamic-pituitary-adrenal axis (HPA) activity and acoustical startle reflex (electromyograms). Specifically, I will acquire the research skills to: (1) Determine the extent to which exposure to acute stress impacts on the relationship between neurobehavior disinhibition (a SUD liability phenotype) and severity of substance use and (2) Clarify the extent to which stress reactivity impacts on the relationship between parental SUD and their offspring's ND. Elucidating the role of stress by taking into account its acute facets along with individual variation in neurobehavioral vulnerability, will point to innovative strategies for prevention and treatment of SUD. By mid-Year 03, I will prepare an R01 application directed at conducting a longitudinal stress study to inform on prevention strategies. ? ? ? ?