Experiencing early-life stress can influence vulnerability to drug addiction in adulthood, and epigenetic marks resulting from stress could contribute to enhanced drug seeking behavior. Rats exposed to daily maternal separation exhibited increased locomotor sensitization to cocaine as adults, indicative of an increased responsivity to the drug. This corresponded with increased DNMT levels in the nucleus accumbens, a brain region involved in the rewarding aspects of addiction (Anier et al., 2014; Cornish and Kalivas, 2000). Further, these animals showed global hypomethylation and hypermethylation of protein phosphatase 1 (PP1) and adenosine A2A receptor (A2AR) genes in the nucleus accumbens. This corresponded with reduced expression of A2AR and PP1 (Anier et al., 2014). Because behavioral sensitization to cocaine has been shown to induce hypermethylation and reduced expression of A2AR and PP1, this study elucidated a potential route through which early-stress could predispose an individual to addiction (Anier et al., 2010). Another study determined that animals with a history of maternal separation began self-administering methamphetamine earlier and self-administered a greater quantity of methamphetamine relative to control animals. This paralleled decreased MeCP2 levels in the
