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

• Published in: Trends in neurosciences (Regular ed.) Vol. 45; no. 12; pp. 955 - 967
• Main Authors: Murphy, Michael D., Heller, Elizabeth A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2022
• Subjects: addiction; Central Nervous System Stimulants - pharmacology; chronic stress; decision-making; DNA Methylation; dorsal striatum; Epigenesis, Genetic; Histones; Humans; Protein Processing, Post-Translational; transposable elements; dorsal striatum; chronic stress; transposable elements; decision-making; addiction
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2022.10.001

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. Stress and stimulant exposure can predispose similar behaviors, including impaired decision-making, cognitive inflexibility, and resilience to updating information; these are governed in part by the dorsal striatum.Epigenetic changes – such as DNA methylation, transposable element activity, and histone post-translational modifications – accumulate as stress or stimulant exposure is maintained from an acute to a chronic condition.Stress or stimulant-induced accumulation of epigenetic changes can potentiate differential gene regulation, altering immediate and future neuronal functions that include exposure-induced synaptic plasticity.Chronic epigenetic dysregulation of regulatory genes in the dorsal striatum may contribute to compulsivity and cognitive inflexibility phenotypes, which are among the hallmarks of anxiety and addiction.