Methylation has been shown to be altered by drugs of abuse. In humans, overall DNA methylation was higher in genomic DNA from lymphocytes of alcoholics than from controls (Bleich et al, 2006; Bonsch et al, 2004), with a concomitant decrease in the expression of the DNA methyltransferases DNMT-3a and DNMT-3b (Bonsch et al, 2006). This same group reported increased DNA methylation in the promoter region of the homocysteine-induced endoplasmic reticulum protein gene HERP (Bleich et al, 2006) and the alpha synuclein gene SNCA in alcoholics (Bonsch et al, 2005). In human lymphoblast cell lines, average overall DNA methylation was found to be significantly associated point-wise, but not overall experiment-wise, with alcohol dependence and nicotine dependence in women, but not in men (Philibert et al, 2008). Methylation levels at 11 CpG sites were also associated point-wise, but not experiment-wise, with nicotine symptom counts. In cultured mouse cortical neurons, chronic ethanol was reported to induce demethylation of CpG islands of the NMDA receptor subunit gene nr2b with a concomitant increase in nr2b expression (Marutha Ravindran and Ticku, 2005). Methylation of the protein
