The Indiana Alcohol Research Center (IARC), established in 1987, has combined research excellence in animal models of alcohol preference, neurochemistry of addiction, biochemistry of alcohol metabolism, molecular biology and genetics of alcohol drinking, and translation of preclinical research findings to the bedside and to the community at large. Studies using an animal model of alcohol abuse initially focused on identifying alcohol-related behaviors, pathways, and neuronal activity and now are focused on correlating genetic variation and changes in mRNA and proteins, with these neurobiological factors. We are now sequencing the genomes of these animals.
The IARC has been a leader in the study of candidate genes (especially ADH1B and ALDH2 variants), and IARC investigators have played central roles in the COGA project. Human studies sponsored by the IARC began with examinations of measures of alcohol responses for heritability and test-retest reliability in twins, followed by correlations between a familial history of alcoholism and personality characteristics, and subjective neuropsychological and electrophysiological responses to alcohol. Current emphasis is on how the alcoholism risk locus at the GABA A2 receptor affects responses to alcohol.
IARC researchers developed alcohol clamping technology, which is critical to teasing out the small effects individual genetic variants have on response to alcohol and permits better application of fMRI and PET imaging to alcoholism studies. The alcohol infusion technology is evolving to provide evolving measures of alcohol craving. These different research programs are now converging to provide an understanding at a molecular and neural pathway level, of how genetic variation influences responses to alcohol and risk of developing alcoholism.