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, Malinovskaja, Aonurm-Helm, Zharkovsky, & Kalda, 2010). Furthermore, infusion of the DNMT inhibitor 5-aza-2-deoxycytidine (5-aza) into the hippocampus or prefrontal cortex was able to attenuate either the acquisition (hippocampus) or expression (prefrontal cortex) of cocaine-induced conditioned place preference behaviors (cocaine reward) in C57BL/6 mice (Han et al., 2010). These examples illustrate the fact that alterations of DNA methylation/demethylation pathways play a role in the phenotypes of drugs of abuse such as cocaine, implicating these pathways in drug addiction mechanisms. The use of DNMT inhibitors enables us to control these pathways pharmacologically and epigenetically modulate target gene expression that control drug phenotypes (Warnault, Darcq, Levine, Barak, & Ron, 2013).
