Alcoholism is characterized by the inability of individuals to regulate their consumption of alcohol appropriately. Considerable evidence links dopaminergic genetic markers like the DRD2 TaqIA polymorphism, which modulates the function and/or expression of dopamine receptors, to the increased risk for developing alcoholism (Noble et al., 2003).
The aims of the proposed pilot study are to acquire preliminary data needed to apply for an NIH grant to assess the relationship between the dopaminergic genetic variants DRD2 TaqIA A1 allele, COMT Val/Val vs. Met, DRD4 VNTR 7-repeat allele and DAT VNTR SCL39 9-repeat (vs. the 10-repeat allele), with central response to alcohol, and associated self-reported mood states in twenty-eight white male social drinkers. For DAT, the variable number of tandem repeat (VNTR) polymorphism of the 3'untranslated region (SLC6A3) will be examined with subgroups that have either the 9/9 or the 10/10 genotype;COMT (catechol-O- methyltransferase) subgroups will be divided based on Val/Val (rapid metabolizers) or Met allele (low metabolizers), DRD2 TaqIA A1 subgroups will be separated into A1+ and A1- participants and the DRD4 VNTR in exon 3 will be separated into subgroups that have either greater or fewer than the 7-repeat allele. We are comparing DA D2-like receptor availability in social drinkers with copies of the above mentioned alleles to those without under two conditions;1.) after ingesting an alcoholic beverage and 2.) after ingesting a placebo beverage. We will contrast the allelic groups with how alcohol alters self-reported mood and use positron emission tomography to measure changes in striatal D2-like dopamine receptor availability (as a marker for dopamine release in response to alcohol) with [18F]fallypride (a radiotracer for D2-like dopamine receptors) to determine whether differences exist based on genotype in response to an alcohol challenge. We expect that the social drinkers with the DRD2 TaqIA A1 allele, DAT with 9 alleles, DRD4 with <7 repeats and the Val/Val COMT genotypes, as compared with their counterparts, will have lower BPND for the radiotracer during the placebo scan and a greater reduction in striatal receptor availability after ingestion of alcohol, relative to their counterparts because, released dopamine will compete with the radiotracer for binding to fewer receptors in the brains of these individuals. To date, there are no published studies examining whether genotype affects the way dopamine receptors respond during an alcohol challenge.
The abuse of and dependence on alcohol continues to be a worldwide epidemic. In the United States 17.3 million adults reported alcohol abuse or dependence and slightly more than half of Americans aged 12 or older reported being current drinkers of alcohol (SAMHSA, 2009). Our proposed study will use non-invasive brain imaging techniques to investigate the role that genetics play in the brain's response to alcohol and possibly the emotional states associated with consuming an alcoholic beverage;with the intention of identifying potential biomarkers that make people vulnerable to harmful drinking behaviors.
