CRACKing the histone code: Cocaine's effects on chromatin structure and function
Open accessAbstract
Epigenetics, the nongenetic component of how chromatin structure influences gene expression, is amazingly complex, and linking how environmental stimuli can influence epigenetic 'gene programs' in specific nerve cells to ultimately control behavior is a seemingly insurmountable puzzle. Cocaine is a highly potent stimulus capable of influencing behavior for the lifetime of an organism. Not surprisingly, psychostimulant-induced epigenetic regulation of gene expression has thus been identified as key to understanding the pathology of addiction. In addition to identifying this essential role of epigenetics in addiction, several important concepts have emerged such as the importance of global, temporal, and spatial control of mRNA expression in considering any given histone modification's influence on a given gene. Adding to this complexity, one has to account for the cumulative influence of other epigenetic modifications on a gene's transcription in addition to the interplay between transcription factors and chromatin structure. This review highlights how bioinformatic, molecular, and behavioral studies on addiction provide new insight into these concepts and outlines two distinct psychostimulant-induced patterns of chromatin regulation which are thought to underlie unique programs of gene expression that contribute importantly to the addicted state.
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Frequency of use is important, as some epigenetic changes occur with short but not repeated drug consumption, as is the case for hyperacetylation of histone H4 along the cFos gene promoter in the striatum, whereas hyperacetylation of histone H3 at BDNF promoters is seen only after repeated cocaine exposure.
“Frequency of use is also important, as some epigenetic changes occur with short but not with repeated drug consumption, as is the case for the hyperacetylation of histone H4 along thecFosgene promoter in the striatum, whereas hyperacetylation of histone H3 at thebrain- derived neurotrophic factor (BDNF) promoters is seen only after repeated cocaine exposure 114 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [114]
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The Neuroscience of Drug Reward and Addiction
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- Authors
- LaPlant, Q., & Nestler, E. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Nestler, Eric J.
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 59
- Issue
- 3
- Pages
- 321-330
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC2948759
- OpenAlex
- W1973754014
- Cited by
- 52
- References
- 46
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 8 · 2012: 10
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (P01DA008227, R01DA007359)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- cocaine, chromatin structure, histone modifications, epigenetics, addiction, psychostimulants, gene expression regulation, transcription factors, spatial and temporal gene regulation, mRNA expression
- MeSH terms
- Animals, Chromatin, Cocaine, Histones, Behavior, Addictive, Chromatin Assembly and Disassembly, Epigenesis, Genetic
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