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Neuron. 2019 Apr 3;102(1):48-59. doi: 10.1016/j.neuron.2019.01.016.

The Molecular Basis of Drug Addiction: Linking Epigenetic to Synaptic and Circuit Mechanisms.

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Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Clinic of Neurology, Departement of Clinical Neurosiences, Geneva University Hospital, Geneva, Switzerland. Electronic address:


Addiction is a disease in which, after a period of recreational use, a subset of individuals develops compulsive use that does not stop even in light of major negative consequences. Here, we review the evidence for underlying epigenetic remodeling in brain in two settings. First, excessive dopamine signaling during drug use may modulate gene expression, altering synaptic function and circuit activity and leading over time to maladaptive behaviors in vulnerable individuals. Second, on a longer timescale, life experience can shape the epigenetic landscape in brain and thereby may contribute to an individual's vulnerability by amplifying drug-induced changes in gene expression that drive the transition to addiction. We conclude by exploring how epigenetic mechanisms might serve as therapeutic targets for addiction treatments.

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