Recent evidence also suggests that epigenetic regulation of gene expression may contribute to the pathogenesis of drug addiction. In the nucleus accumbens of rodents, cocaine increased histone acetylation of promoters in a number of genes (cfos, fos-b, bdnf, cdk5, npy) that are known to be important in the addiction process (reviewed in (18), Supplementary Table 1). Also, higher methylation levels in the promoter region of OPRM1 have been found in the lymphocytes of former long-term heroin addicts undergoing methadone maintenance treatment (19). Alcohol withdrawal increased expression of histone deacetylases, and decreased expression of CREB and NPY in the amygdala in rodent models, while inhibition of histone deacetylases reduced the anxiety resulting from alcohol withdrawal (20). Thus, variability in these gene regulators may be additional important determinants of drug addiction phenotypes.
