This research has been done so as to understand the Exposure to drugs of abuse produces robust transcriptional and epigenetic reorganization within brain reward circuits that outlives the direct effects of the drug and may contribute to addiction. Addiction is an increasingly prevalent problem in the United States, associated with progressively higher rates of morbidity and mortality. Experience with drugs of abuse results in significant transcriptional and epigenetic alterations in the nucleus accumbens (NAc) that support both synaptic and behavioral plasticity, outlasting the direct effects of the drug and contributing to the development of addiction. DNA methylation is a covalent epigenetic modification that is altered following stimulant exposure and is critical for behavioral and physiological adaptations to drugs of abuse. These data suggest complex temporal dynamics in the regulation of DNA methylation machinery. In rats that chronically self-administered cocaine, DNMT3A expression in the NAc was downregulated 24 hr after the last cocaine infusion. Although activity-related loss of DNA methylation requires the Gadd45 (Growth arrest and DNA-damage-inducible) gene family, very little is known about how this family regulates activity within the nucleus accumbens or behavioral responses to drugs of abuse. Finally, we conclude demonstrating that Gadd45b knockdown decreases striatal neuron action potential burst duration in vitro, without altering other electrophysiological characteristics. These results suggest that striatal Gadd45b functions as a dopamine-induced gene that is necessary for cocaine reward memory and DRD1-mediated transcriptional activity.