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Transcriptional and epigenetic mechanisms of addiction

Alfred J Robison1, Eric J Nestler

  • 1Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, BOX 1065, New York, New York 10029, USA.

Nature Reviews. Neuroscience
|October 13, 2011
PubMed

Insights

Chronic drug exposure alters brain gene regulation, contributing to addiction. Understanding these changes in transcriptional potential offers new therapeutic strategies for addiction treatment.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Chronic drug abuse leads to lasting changes in brain structure and function.
  • These alterations are linked to modifications in gene regulation, contributing to the addictive phenotype.

Purpose of the Study:

  • To review the mechanisms by which drugs of abuse alter gene transcriptional potential.
  • To highlight the role of gene regulation in the neurobiological underpinnings of addiction.

Main Methods:

  • Review of existing literature on drug-induced gene regulation.
  • Analysis of transcriptional machinery and epigenetic modifications.
  • Inclusion of transcription factors (ΔFOSB, CREB, NF-κB) and non-coding RNAs.

Main Results:

  • Drugs of abuse modify gene expression through various mechanisms.
  • Key mechanisms include altering transcriptional machinery and epigenetic landscapes.
  • Histone modifications, DNA methylation, and non-coding RNAs play significant roles.

Conclusions:

  • Gene regulatory alterations are central to the persistent brain changes caused by drug addiction.
  • These insights provide potential novel therapeutic targets for addiction interventions.

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