Grant: Operating Grant

Drug dependence is a significant worldwide public health problem. Drug abusers suffer from physical, psychological, financial and legal problems, and society as a whole is affected by increased health care costs, crime, violence and a toll on children and families. It is now well recognized the public health threats such as infectious diseases (tuberculosis, HCV and HIV) and sexually transmitted diseases are on the rise among drug users in general. Cocaine dependence in particular makes up a significant proportion of clinical case loads; it is a chronic and severe disorder characterized by compulsive drug-seeking and continued drug use despite negative consequences. Over the past 3 decades, a large body of research has provided strong evidence that drug dependence is heritable. In previous CIHR-funded research, the applicant utilized behavioural genetic techniques to demonstrate that inbred mouse strains such as the A/J and C57BL/6J (B6) show heritable differences in their responses to alcohol, cocaine, morphine and nicotine. The B6 strain shows significantly higher cocaine sensitivity as measured by psychomotor activation as well as higher intravenous cocaine self-administration compared to the A/J. Genetic analyses identified Dcc gene on chromosome 18 as a very strong candidate gene related to the differences between the strains (Boyle & Gill, 2009). The Dcc gene is highly expressed in mesocorticolimbic dopamine neurons, the primary site of cocaine's actions in the brain. The objective of the proposed research is to further examine the role of the Dcc gene in mediating individual differences in cocaine sensitivity and intravenous cocaine self-administration, using a mouse model.