Alcohol Dependence and Genes Encoding α2 and γ1 GABAA Receptor Subunits: Insights from Humans and Mice

One approach to identifying the causes of alcoholism, particularly without crossing ethical boundaries in human subjects, is to look at the person’s genome (and particularly at the variations that naturally arise in the DNA) to identify those variations that seem to be found more commonly in people with the disease. Some of these analyses have focused on the genes that encode subunits of the receptor for the brain chemical (i.e., neurotransmitter) γ-aminobutyric acid (GABA). Different epidemiological genetic studies have provided evidence that variations in certain GABA(A) receptor (GABA(A)-R) subunits, particularly subunits α2 and γ1, are correlated with alcohol dependence. Manipulations of these genes and their expression in mice and rats also are offering clues as to the role of specific GABA(A)-Rs in the molecular mechanisms underlying alcoholism and suggest possibilities for new therapeutic approaches.