Cited by 409Neurotransmitter Receptor Influence on BehaviorGenomics and Chromatin DynamicsSubstance Abuse Treatment and Outcomes

Genome-wide Analysis of Chromatin Regulation by Cocaine Reveals a Role for Sirtuins

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Renthal, William, Kumar, Arvind, Xiao, Guanghua, Wilkinson, Matthew, Covington, Herbert E., Maze, Ian, Sikder, Devanjan, Robison, Alfred J. +9 more·2009·Neuron

Abstract

Changes in gene expression contribute to the long-lasting regulation of the brain's reward circuitry seen in drug addiction; however, the specific genes regulated and the transcriptional mechanisms underlying such regulation remain poorly understood. Here, we used chromatin immunoprecipitation coupled with promoter microarray analysis to characterize genome-wide chromatin changes in the mouse nucleus accumbens, a crucial brain reward region, after repeated cocaine administration. Our findings reveal several interesting principles of gene regulation by cocaine and of the role of DeltaFosB and CREB, two prominent cocaine-induced transcription factors, in this brain region. The findings also provide comprehensive insight into the molecular pathways regulated by cocaine-including a new role for sirtuins (Sirt1 and Sirt2)-which are induced in the nucleus accumbens by cocaine and, in turn, dramatically enhance the behavioral effects of the drug.

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Crossref · 10.1016/j.neuron.2009.03.026

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  • Acute and chronic drug exposures (stimulants, opioids, alcohol, nicotine) increase total cellular levels of acetylation of histones H3 and H4, apparently by unbalancing HAT and HDAC function.

    “These studies have shown that acute and chronic drug exposures (stimulants, opioids, alcohol, nicotine) increase total cellular levels of acetylation of histones H3 and H4 105- 110 , apparently by unbalancing HAT and HDAC function.”

    From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [108]

    The Results section on histone acetylation in the nucleus accumbens reports that chronic cocaine increased H3 and H4 acetylation at many gene promoters. It does not establish increased total cellular acetylation, effects of acute exposure or of opioids, alcohol, and nicotine, or a HAT–HDAC imbalance as the cause. Page numbers are not available in our copy. (LLM, conf=0.88)

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Authors
Renthal, W., Kumar, A., Xiao, G., Wilkinson, M., Covington, H. E., Maze, I., Sikder, D., Robison, A. J., LaPlant, Q., Dietz, D. M., Russo, S. J., Vialou, V., Chakravarty, S., Kodadek, T. J., Stack, A., Kabbaj, M., & Nestler, E. J.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • Florida State University (US)
Corresponding author
Nestler, Eric J.
Venue
Neuron
Publisher
Elsevier BV
Published
2009-05
Volume
62
Issue
3
Pages
335-348
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2080585999
Cited by
409
References
68
Citations by year
2026: 7 · 2025: 11 · 2024: 15 · 2023: 19 · 2022: 19 · 2021: 29 · 2020: 16 · 2019: 25 · 2018: 28 · 2017: 25 · 2016: 28 · 2015: 17 · 2014: 35 · 2013: 29 · 2012: 37
FWCI
14.69
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Drug Abuse (P01DA008227, R01DA007359, R01DA014133)
Topics
  • 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
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
cocaine, chromatin regulation, sirtuins, SIRT1, SIRT2, ΔFosB, CREB, nucleus accumbens, drug addiction, reward systems, transcriptional regulation, gene expression, repeated cocaine administration
MeSH terms
Animals, Chromatin, Cocaine, Gene Expression Regulation, Male, Mice, Inbred C57BL, Nucleus Accumbens, Promoter Regions, Genetic, Reinforcement, Psychology, Signal Transduction, Proto-Oncogene Proteins c-fos, Cyclic AMP Response Element-Binding Protein, Dopamine Uptake Inhibitors, Oligonucleotide Array Sequence Analysis, Feedback, Physiological, Sirtuins, Mice, Genome-Wide Association Study

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