Teenagers, Drug Addiction, and Reward and Impulse Control

Background: Even under similar drug use patterns, the risk for drug addiction varies from individual to individual. However, the neurobiological mechanisms underlying this variability are poorly understood and characterized. Studies suggest that certain traits observed in substance dependent individuals may actually precede drug use, and could augur future substance dependence. Understanding how the presence of these traits increases vulnerability to substance addiction could aid in the development of early intervention, preventative measures, as well as better treatment strategies. Objective: The primary goal of this protocol is to improve our understanding of increased susceptibility to developing substance addiction. We focus here on reward and punishment learning, and impulse control, with an emphasis on the underlying role of dopamine and serotonin function in these two cognitive functions. Further, given that cortical plasticity is enhanced during childhood and adolescence, we begin to address whether early exposure to substances enhances neurobiological changes that make an individual vulnerable to subsequent substance addiction. Subject Population: We focus on adolescents (13-17 years old) with known increased vulnerability to substance addiction individuals with early exposure to substances, i.e. , those who have used drugs on multiple occasions before the age of 15, and those diagnosed with conduct disorder and who are not as yet substance dependent, along with matched controls. Experimental Design: This study involves cognitive, pharmacological and functional magnetic resonance imaging (fMRI) testing in a mixed, within/between-subject design. Based upon power analyses, we estimate needing 30 participants in each of 4 groups early exposure (EE), conduct disorder (CD-NE), conduct disorder with early exposure (CD-EE), and controls with no early exposure (NE) to complete the experiment. This is a within subjects, placebo controlled, crossover design with participants tested before and after 1) cabergoline (D2 receptor agonist) treatment, 2) acute tryptophan depletion, and 3) placebo. Outcome Measures: The primary outcome measures will be BOLD fMRI activation and behavioral performance on various cognitive tasks that deal with impulse control and reward learning before and after each of the three treatments listed above. Secondary outcome measures include gene x environment interactions and stress and novelty-seeking measures.