PET IMAGING OF BRAIN OPIOID RECEPTORS IN ALCOHOLISM

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Alcohol abuse and alcoholism is a major public health problem in the United States, but little is known of the neurochemical pathways in the human brain that mediate the reinforcing and other properties of ethanol. The brain's endogenous opioid system is known to play an important role in reward mechanisms and recently it has been targeted in treatment efforts using the opiate antagonist naltrexone. The rationale for using opioid blockade in the treatment of alcoholism is well founded in experimental animal models of human alcohol use and abuse, but we know little about the underlying differences in the endogenous opioid system between healthy individuals and alcoholics. Positron emission tomography (PET) is a non-invasive imaging method that can be used to image and quantitate a number of neuromarkers and mu opioid receptors can be imaged in the human brain by PET using the well-validated ligand C-11 carfentanil. Our long-term goal is to better understand the function of the endogenous brain opioid system in alcohol use and abuse, and determine if it is involved in increasing the risk of alcoholism. The use of PET to measure regional mu opioid receptors is an approach that could provide new insight into the role of the endogenous opioid system in alcoholism. The specific aims of this study are: l) Measure regional mu opioid receptor binding by PET in non-alcoholic men and women with a positive family history of alcoholism.; 2) Measure regional brain mu opioid receptor binding by PET in FHP and FHN alcoholic men and women and relate regional binding to behavioral measures of alcohol abuse; and 3) Measure the change in regional mu opioid receptor binding during one month controlled abstinence from ethanol in alcoholic men and women.