Of the glutamate receptors, the NMDA receptors are most sensitive to ethanol and are partially inhibited by clinically relevant ethanol concentrations (starting from 20 mM) (Lovinger et al., 1989). How the ethanol's inhibition of the glutamate receptors translates to altered expression of the receptor subunits is not understood. As the NMDA receptors are involved in many physiological processes such as neuronal signal transduction, LTP, long-term depression (LTD), excitotoxicity (also in alcohol withdrawal phase), and neuronal survival, their altered function in alcoholics may directly or indirectly affect gene regulation in general and transcription of specific genes in some neurons. Epidemiological evidence indicates that more than 50% of the risk for becoming an alcoholic stems from genetic susceptibility (Kalsi et al., 2009). Many glutamate receptor genes have been identified as risk genes for alcoholism and alcohol-related phenotypes in human studies, including the GluN2A, the mRNA expression of which was now down-regulated in the caudate of alcoholics in this study (Wernicke et al., 2003; Petrakis et al., 2004; Rujescu et al., 2005; Kim et al., 2006; Preuss et al., 2006; Ray et al.,
