In conclusion, our study has shown that, at least within the hippocampus, chronic alcohol and cocaine exposure results in both overlapping and specific changes in expression of GABAergic genes. Similar findings in addiction-vulnerable rats provide clues as to predisposing factors for alcohol and drug addiction. The selected GABAergic genes were strong candidates for involvement in addiction and in addictive tendencies. Indeed, 14/25 of the human genes (global p = 9.1×10−14) and 12/25 of the rat genes (global p = 7.0×10−11) showed nominally significant changes in gene expression. Moreover, there was striking overlap in human and rat genes that showed no changes in expression; for example of the genes encoding the GABAA receptor subunits, changes were largely confined to genes encoding the gamma subunits and not the alpha or beta subunits (other than alpha2 in the alcoholics). Finally, it is remarkable that such strong and consistent findings were evident in the ‘snapshot in time’ captured in the human mRNA transcripts bearing in mind that other factors that might alter gene expression including lifetime stressors were unknown.
