This project evaluates the effects of the presence of genetic polymorphisms (especially the A1 allele) and of chronic ingestion of alcohol on the dopamine D2 receptors (DRD2) in vivo by studying subjects who meet the DSM III-R criteria for alcoholism. The study is aimed at evaluation of the sustained effects of chronic alcoholism on the DRD2 receptors, hence, subjects will be studied following two weeks of alcohol abstinence. This will exclude any confounding acute effects of alcohol on DRD2 receptors. The subjects will be subtyped by Cloninger's Type I and II criteria, age of onset, antisocial personality, RDC criteria, MAST and SAD-Q scores. Genetic typing will include three informative methods--restriction fragment length polymorphism (RFLP), the polymerase chain reaction-- single strand conformation polymorphism (PCR-SSCP) and the dinucleotide microsatellite polymorphism (CA/TG Repeats). The frequency of polymorphisms in alcoholic subjects will be compared with a control (nonalcoholic) group. Proven positron emission computed tomographic imaging (PET) will be used to quantify dopamine-D2 receptor density (Bmax) and dissociation constant (Kd) in the caudate nucleus, in vivo, in the above alcoholics who have been genetically typed. The receptor measurements in subjects with A1 allele will be compared to those who do not demonstrate the presence of A1 allele, irrespective of the alcoholic status. The receptor measurements in alcoholics will be compared with nonalcoholic, irrespective of the allele status. In this project, the following hypotheses will be tested: Primary: 1. There is a significant decrease in DRD3 Bmax and Kd in he caudate nuclei in alcoholic and nonalcoholic subjects with A1 allele versus those without the A1 allele. 2. There is a significant decrease in the Kd in alcoholic subjects versus nonalcoholic subjects, regardless of their allele status. Secondary 1. The frequency of certain polymorphisms of the DRD2 gene (especially the A1 allele) are significantly higher in alcoholics as compared to nonalcoholic. 2. There is a significant decrease in the dissociation constant (Kd) of the DRD2 receptors in the caudate nuclei in specific subtypes of alcoholism 3. There is a significant increased frequency of DRD2 polymorphisms in specific subtypes of alcoholism.
