Grant: Project Grant

A major difficulty in the treatment of drug addiction is the high rate of relapse following periods of abstinence. There is strong evidence that exposure to stressful incidents (like an argument with one's spouse) 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 advanced our understanding of the neuronal circuits that are involved stress-induced relapse to drugs. However, translation of findings from these animal models to addiction treatments has proven to be quite difficult. A possible reason might be a limited success of current models to properly reflect critical aspects of human addiction. Consequently, there has been an increased interest in the development of models for drug relapse following voluntary abstinence, and particularly procedures that incorporate potential negative outcome to drug seeking. We have recently established a rodent model of stress-induced relapse following voluntary abstinence imposed by punishment of drug seeking behaviour. We found that exposure to an ecologically relevant stressor, acute food deprivation, produces a robust relapse to heroin seeking, in the abstinent rats. Here we propose to use this model with a range of behavioural, neurochemical, and pharmacological techniques to identify the brain systems that are critically involved in stress-induced relapse to drug seeking in voluntarily 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 fasting, to interact with brain systems that are critical for relapse. Ultimately, and together with other relevant findings, these insights may inform and facilitate the development of prevention and intervention strategies for the treatment of drug addiction.