Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Addiction is a very complex and heterogeneous disorder. To address this complexity, an important goal of current addiction research is to understand the behavioral, cognitive, biological, personality, and genetic mechanisms that mediate the transition from initial drug use to drug addiction as well as the neurobiological and sex/gender bases associated with individual vulnerability to addiction. For example, personality studies indicate that people characterized by impulsivity, sensation-seeking and other traits exhibit a relatively greater probability of becoming addicted. At the same time, biological studies indicate that addiction is in fact a learning disorder: All addictive drugs act on a neural system for reinforcement learning called the midbrain dopamine system, which projects to and regulates the brain's system for cognitive control, called frontal cortex. The addictive consequences of substance use are felt both over the short-term, by enhancing the potency of the dopamine system during consumption, and over the long-term, by rewiring neural connections in frontal cortex. Further, the development and expression of the dopamine system is determined in part by genetic factors that vary across individuals such that dopamine-related genes are partly responsible for addiction-proneness. Finally, effects of gonadal hormones on the dopamine reward system are postulated to have important implications for gender differences in susceptibility to addiction. Despite decades of research, a causal model of addiction that incorporates these multiple levels of analysis remains to be created. In this project, we propose to use a combination of behavioral and electrophysiological experiments, sex-based analysis and genetics to investigate these neural mechanisms in both abusers and non-abusers. In so doing we hope to identify biological factors underlying substance abuse that will be amenable to novel therapies for drug addiction.