Epigenetics and substance use disorders: translational aspects

Substance use disorders (SUDs) are characterized by a loss of control over substance use behaviors and continued use in the face of adverse consequences. SUD is diagnosed on the basis of behavioral changes in the affected individual that emerge over the course of substance use experience. As such, the field of SUD research has come to appreciate that the emergence of SUDs is driven, in part, by long-lasting substance-induced changes in brain function in key reward regions. Changes in the epigenetic state within the nuclei of brain cells that comprise brain reward regions are one molecular mechanism by which substance use experience can drive lasting changes in brain function. Epigenetics describes adaptable regulatory mechanisms that affect DNA-related processes, such as gene expression, without affecting the code of the DNA sequence itself. Most importantly, these epigenetic mechanisms are dynamic and highly sensitive to the experience of substance use. Here, we review the recent literature on the epigenetics of SUDs. We focus this chapter on the SUD-related research of the most studied posttranslational modifications of histones (histone acetylation and methylation), DNA methylation, nonprotein coding RNA, and transcription factors. We go on to discuss the emerging field of neuroepigenetic editing and discuss the translational utility of these and other laboratory approaches to deliver much-needed treatments for the growing population of individuals suffering from SUDs.