Grant: Operating Grant

About 4% of Canadian adults are dependent on alcohol, and there is a much higher percentage that misuses alcohol. This has a very high cost to society in terms of increased mortality both directly and indirectly related to alcohol consumption, lost productivity, absenteeism and health care and crime-related costs. One of the strongest factors leading to increased alcohol intake and relapse is stress. A better understanding of the neural pathways that produce stress-induced relapse would aid in the development of more effective treatments for relapse prevention that would help to alleviate these problems. We have modeled stress-induced relapse in laboratory rodents that have been trained to drink alcohol. We propose these experiments to help understand the brain mechanisms that cause such stress-induced relapse. We found that prazosin, a drug that acts by blocking receptors normally stimulated by the stress-responsive brain chemical noradrenaline, reduces stress-induced relapse. Alcohol dependence changes how animals and humans respond to stress as well as to drugs. We will therefore see if alcohol dependent rats show greater stress relapse, and whether dependence changes the effects of prazosin on relapse caused by stress. Then we will find the brain areas in which prazosin acts to reduce relapse induced by stress. The remaining experiments will provide more detailed information on how the brain cells in these areas cause relapse. Our proposal will provide important, timely data on the brain mechanisms involved in stress-induced relapse that will help refine relapse prevention treatments currently used, or indicate potential new treatments.