Emerging Role of Epigenetic Mechanisms in Alcohol Addiction

Alcohol Clin Exp Res. 2017 Apr;41(4):666-680. doi: 10.1111/acer.13338. Epub 2017 Feb 18.

Abstract

Alcohol use disorder (AUD) is a complex brain disorder with an array of persistent behavioral and neurochemical manifestations. Both genetic and environmental factors are known to contribute to the development of AUD, and recent studies on alcohol exposure and subsequent changes in gene expression suggest the importance of epigenetic mechanisms. In particular, histone modifications and DNA methylation have emerged as important regulators of gene expression and associated phenotypes of AUD. Given the therapeutic potential of epigenetic targets, this review aims to summarize the role of epigenetic regulation in our current understanding of AUD by evaluating known epigenetic signatures of brain regions critical to addictive behaviors in both animal and human studies throughout various stages of AUD. More specifically, the effects of acute and chronic alcohol exposure, tolerance, and postexposure withdrawal on epigenetically induced changes to gene expression and synaptic plasticity within key brain regions and the associated behavioral phenotypes have been discussed. Understanding the contribution of epigenetic regulation to crucial signaling pathways may prove vital for future development of novel biomarkers and treatment agents in ameliorating or preventing AUD.

Keywords: Alcoholism; Amygdala; Anxiety; DNA Methylation; Epigenetics; Histone Acetylation; Histone Methylation.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcoholism / diagnosis
  • Alcoholism / genetics*
  • Alcoholism / metabolism*
  • Animals
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA Methylation / physiology
  • Epigenesis, Genetic / physiology*
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism
  • Humans

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Histone Acetyltransferases