Grant: Operating Grant

Addiction is the most common psychiatric disorder of our era. It accounts for 12% of deaths worldwide, and costs Canadians nearly $40 billion per year. In spite of much research, medications approved for drug addiction are lacking. This is in part because preclinical tests are typically conducted in animals that take drugs, but that do not show addiction-like traits. Animals that simply take drugs are not necessarily 'addicted'. The reliance on such animals to study addiction might have misled us regarding the neurobiology of addiction. With CIHR funding, we have refined a new model whereby rats taking rapid intravenous cocaine injections show excessive motivation to obtain the drug, whereas rats taking slower injections do not. Thus, by varying the speed of drug delivery, we have in our hands a powerful model whereby two groups of rats take cocaine, but only one group shows an addiction phenotype. Studying these two groups represents a unique window of opportunity to hone in on a fundamental question; what is the difference between a drug-taking brain and a drug-addicted brain? Based largely on studies using animals that self-administer drugs, it has been suggested that addiction might involve a hyperactive orbitofrontal cortex (a brain area involved in the evaluation of rewards) and changes in the activity of two molecules in the downstream dorsal striatum (a brain area involved in the pursuit of rewards). These molecules are the neurotrophin BDNF and the neurotransmitter glutamate. But are these changes truly linked to addiction, or are they simply a consequence of taking drugs? Here I propose to use our unique model to address this. In essence, we will use variation in the speed of drug injection as a tool to parse the neurobiology of addiction from the neurobiology of mere drug taking. This is certain to better our understanding of how addiction evolves, and how it might be treated.