Epigenetics and Addiction

Peter J. Hamilton, Eric J. Nestler
Nash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029

As an individual becomes addicted to a drug of abuse, nerve cells within the brain’s reward circuitry adapt at the epigenetic level during the course of repeated drug exposure. These drug-induced epigenetic adaptations mediate enduring changes in brain function which contribute to life-long, drug-related behavioral abnormalities that define addiction. Targeting these epigenetic alterations will enhance our understanding of the biological basis of addiction and might even yield more effective anti-addiction therapies. However, the complexity of the neuroepigenetic landscape makes it difficult to determine which drug-induced epigenetic changes causally contribute to the pathogenic mechanisms of drug addiction. In this review, we highlight the evidence that epigenetic modifications, specifically histone modifications, within key brain reward regions are correlated with addiction. We then discuss the emerging field of locus-specific neuroepigenetic editing, which is a promising method for determining the causal epigenetic molecular mechanisms that drive an addicted state. Such approaches will substantially increase the field’s ability to establish the precise epigenetic mechanisms underlying drug addiction, and could lead to novel treatments for addictive disorders.