Consistent with PA-08-217, Drug Abuse Prevention Intervention Research, we propose to study neurobiological mechanisms that underlie currently recognized commonalities in behavioral manifestations of attention deficit hyperactivity disorder (ADHD) and drug addiction. Alterations in cortical dopamine systems may play a prominent role in ADHD, and that the beneficial effects of stimulant therapies (e.g. methylphenidate (MPH), amphetamines) lies in their ability to reduce abnormalities in prefrontal dopamine function. In this competitive renewal, we would like to continue our work on the relationship between stimulant therapy in juvenile rats and later drug-seeking behavior. Here, we will build upon our findings to: 1) directly confirm our preliminary observations regarding untoward later consequences of abnormalities in juvenile cortical dopamine function; 2) continue to explore gender-related differences in the effects of early stimulant treatment; and 3) further define dopaminergic consequences of stimulant exposure during the juvenile period that may underlie later behavioral attributes of addiction. We will use behavioral, neurochemical, and neuroanatomical approaches to investigate prefrontal dopamine function and the emergence of substance abuse-related problems. Most importantly, we will use this information to develop new, preventative strategies that may be used to reduce drug abuse in this high-risk population.