Cited by 599Histone Deacetylase Inhibitors ResearchNeurotransmitter Receptor Influence on BehaviorGenomics and Chromatin Dynamics

Histone Deacetylase 5 Epigenetically Controls Behavioral Adaptations to Chronic Emotional Stimuli

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Renthal, William, Maze, Ian, Krishnan, Vaishnav, Covington, Herbert E., Xiao, Guanghua, Kumar, Arvind, Russo, Scott J., Graham, Ami +9 more·2007·Neuron

Abstract

Previous work has identified alterations in histone acetylation in animal models of drug addiction and depression. However, the mechanisms which integrate drugs and stress with changes in chromatin structure remain unclear. Here, we identify the activity-dependent class II histone deacetylase, HDAC5, as a central integrator of these stimuli with changes in chromatin structure and gene expression. Chronic, but not acute, exposure to cocaine or stress decreases HDAC5 function in the nucleus accumbens (NAc), a major brain reward region, which allows for increased histone acetylation and transcription of HDAC5 target genes. This regulation is behaviorally important, as loss of HDAC5 causes hypersensitive responses to chronic, not acute, cocaine or stress. These findings suggest that proper balance of histone acetylation is a crucial factor in the saliency of a given stimulus and that disruption of this balance is involved in the transition from an acute adaptive response to a chronic psychiatric illness.

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Crossref · 10.1016/j.neuron.2007.09.032

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Authors
Renthal, W., Maze, I., Krishnan, V., Covington, H. E., Xiao, G., Kumar, A., Russo, S. J., Graham, A., Tsankova, N., Kippin, T. E., Kerstetter, K. A., Neve, R. L., Haggarty, S. J., McKinsey, T. A., Bassel-Duby, R., Olson, E. N., & Nestler, E. J.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • University of California, Santa Barbara (US)
  • Harvard University (US)
Corresponding author
Nestler, Eric J.
Venue
Neuron
Publisher
Elsevier BV
Published
2007-11
Volume
56
Issue
3
Pages
517-529
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2104261628
Cited by
599
References
55
Citations by year
2026: 5 · 2025: 9 · 2024: 13 · 2023: 17 · 2022: 26 · 2021: 26 · 2020: 19 · 2019: 26 · 2018: 26 · 2017: 37 · 2016: 47 · 2015: 38 · 2014: 55 · 2013: 51 · 2012: 50
FWCI
14.56
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Texas Southwestern Medical Center
  • Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
  • National Institute on Drug Abuse
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
HDAC5, histone acetylation, epigenetic regulation, cocaine, chronic stress, nucleus accumbens, chromatin structure, gene expression, drug addiction, depression, behavioral adaptation, stimulus salience, class II HDACs
MeSH terms
Acetylation, Adaptation, Physiological, Animals, Chromatin, Chronic Disease, Cocaine, Disease Models, Animal, Emotions, Histone Deacetylases, Histones, Mice, Inbred C57BL, Nucleus Accumbens, Reward, Stress, Psychological, Gene Expression Regulation, Enzymologic, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Epigenesis, Genetic, Mice

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