Drugs of abuse such as cocaine also regulate DNA methylation pathways. Cocaine exposure causes a complex expression pattern of DNMT3a expression. There was a biphasic response in that early induction of DNMT3a in the nucleus accumbens (NAc), was followed by down-regulation upon both acute and chronic cocaine exposure. During chronic cocaine exposure, a persistent and stable enhancement was observed in the NAc suggesting a role for DNMTs in the homeostatic feedback regulation of cocaine-mediated effects (LaPlant et al., 2010). Striatal MeCP2 was induced by cocaine self-administration and shown to positively regulate BDNF expression by a homeostatic regulation via microRNA-212 (Im, Hollander, Bali, & Kenny, 2010). MeCP2 signaling in the NAc is also involved in the behavioral responses to psychostimulants such as amphetamines (Deng et al., 2010). The induction of DNMT3a and 3b in the NAc by acute cocaine exposure was shown to increase binding of MeCP2 at the protein phosphatase-1 catalytic subunit promoter implicating DNMT involvement in the behavioral sensitization to cocaine. Consequently, use of the DNMT inhibitor zebularine was able to delay the onset of cocaine behavioral sensitization (Anier,
