Epigenetics of Drug Addiction

Abstract

Substance use disorders (SUDs) are chronic brain diseases characterized by transitions from recreational to compulsive drug use and aberrant drug craving that persists for months to years after abstinence is achieved. The transition to compulsive drug use implies that plasticity is occurring, altering the physiology of the brain to precipitate addicted states. Epigenetic phenomena represent a varied orchestra of transcriptional tuning mechanisms that, in response to environmental stimuli, create and maintain gene expression–mediated physiological outcomes. Therefore, epigenetic mechanisms represent a convergent regulatory framework through which the plasticity required to achieve an addicted state can arise and then persist long after drug use has ended. In the first section, we will introduce basic concepts in epigenetics, such as chromatin architecture, histones and their posttranslational modifications, DNA methylation, noncoding RNAs, and transcription factors, along with methods for their investigation. We will then examine the implications of these mechanisms in SUDs, with a particular focus on cocaine-mediated neuroepigenetic plasticity across multiple behavioral models of addiction.