Convergent actions of stress and stimulants via epigenetic regulation of neural circuitry

Abstract

The dorsal striatum integrates prior and current information to guide appropriate decision-making. Chronic stress and stimulant exposure interferes with decision-making, and can confer similar cognitive and behavioral inflexibilities. This review examines the literature on acute and chronic regulation of the epigenome by stress and stimulants. Recent evidence suggests that exposures to stress and stimulants share similarities in the manners in which they regulate the dorsal striatum epigenome through DNA methylation, transposable element activity, and histone post-translational modifications. These findings suggest that chronic stress and stimulant exposure leads to the accumulation of epigenetic modifications that impair immediate and future neuron function and activity. Such epigenetic mechanisms represent potential therapeutic targets for ameliorating convergent symptoms of stress and addiction.

Keywords: addiction; chronic stress; decision-making; dorsal striatum; transposable elements.