Grant: Operating Grant

Substance abuse is a major public health concern: In Canada, tobacco alone is consumed by an estimated 15-20% of the population, and 20% of all drinkers engage in hazardous alcohol use. The total cost to society--in terms of the burden placed on the Canadian health care system, law enforcement, and workplace productivity--is estimated to be about $40 billion per year. But why is it that only some people who use drugs actually become addicted? Can sufficient exposure to substances of abuse cause anyone to become dependent or do addicts simply lack the will-power to resist? In fact, addiction depends on a far more complicated process involving a confluence of biological, behavioral, cognitive, social, and personality-related factors. Notably, 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. 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. We have recently found that young adults who are dependent on substances of abuse produce an abnormal brainwave response to reinforcing events, and further, that they behave abnormally on a decision making task that is diagnostic of dopamine dysfunction. In this project, we propose to conduct a series of experiments that will investigate whether this atypical brain response is 1) associated with abnormal reinforcement learning, 2) elicited by drug rewards, 3) present in adolescence even before acute drug use, and 4) associated with genes that code for the expression of the dopamine system. In so doing we hope to tease apart biological, cognitive and personality-related factors underlying substance abuse that will be amenable to treatment.