Grant: Project Grant

A major difficulty in the treatment of heroin and cocaine addiction is the high rate of relapse to drug use following periods of abstinence. Clinical studies suggest that exposure to either acute stress (like an argument with a co-worker) or more chronic adverse life events (for example, prolonged unemployment) is associated with subsequent drug relapse. While studies in humans highlight the contribution of stress to drug relapse, the underlying neurobiological mechanisms are not clear. Animal models of drug taking and relapse have made considerable contributions towards the elucidation of the neuronal circuits that are involved in acute stress-induced relapse to drugs. However, there is surprisingly little information on the impact of exposure to chronic stress on drug seeking following prolonged withdrawal and the underlying neural mechanisms. In my laboratory, we have established a rodent model of drug seeking to study the effects of an ecologically relevant chronic stressor, chronic food restriction, on heroin and cocaine seeking upon re-exposure to the drug-taking environment and associated cues. Using this procedure, we found that exposure to mild food restriction produces a robust augmentation of heroin and cocaine seeking, compared to sated controls. Here we propose to use this model with a range of behavioural, neurochemical, and molecular techniques to identify the brain systems that are critically involved in chronic stress-induced augmentation of drug seeking in abstinent rats. The new knowledge gained through these studies will contribute greatly to our understanding of the neural mechanisms that allow common environmental challenges, such as chronic stress, to interact with brain systems that are critical for relapse. Ultimately, these insights may inform and facilitate the development of prevention and intervention strategies for the treatment of drug addiction.