Abstract
Drug-induced changes in gene expression likely contribute to long-lasting structural and functional alterations in the brain’s reward circuitry and the persistence of addiction. Modulation of chromatin structure through covalent histone modifications has emerged as an important regulator of gene transcription in brain and increasing evidence suggests that misregulation of histone acetylation contributes to the establishment and maintenance of aberrant neuronal gene programs and behaviors associated with cocaine or amphetamine exposure. In this review, we summarize evidence supporting a role for histone acetylation in psychostimulant-induced plasticity and discuss findings from preclinical studies investigating histone deacetylase (HDAC) action and the use of small-molecule HDAC inhibitors (HDACis) to correct drug-mediated transcriptional dysregulation.
Keywords: Chromatin, drug addiction, histone acetylation, histone deacetylase (HDAC), histone methyltransferase (HMT), plasticity.
CNS & Neurological Disorders - Drug Targets
Title:Histone Deacetylases as Potential Targets for Cocaine Addiction
Volume: 14 Issue: 6
Author(s): Pamela J. Kennedy and Eric Harvey
Affiliation:
Keywords: Chromatin, drug addiction, histone acetylation, histone deacetylase (HDAC), histone methyltransferase (HMT), plasticity.
Abstract: Drug-induced changes in gene expression likely contribute to long-lasting structural and functional alterations in the brain’s reward circuitry and the persistence of addiction. Modulation of chromatin structure through covalent histone modifications has emerged as an important regulator of gene transcription in brain and increasing evidence suggests that misregulation of histone acetylation contributes to the establishment and maintenance of aberrant neuronal gene programs and behaviors associated with cocaine or amphetamine exposure. In this review, we summarize evidence supporting a role for histone acetylation in psychostimulant-induced plasticity and discuss findings from preclinical studies investigating histone deacetylase (HDAC) action and the use of small-molecule HDAC inhibitors (HDACis) to correct drug-mediated transcriptional dysregulation.
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Cite this article as:
Kennedy J. Pamela and Harvey Eric, Histone Deacetylases as Potential Targets for Cocaine Addiction, CNS & Neurological Disorders - Drug Targets 2015; 14 (6) . https://dx.doi.org/10.2174/1871527314666150529144804
DOI https://dx.doi.org/10.2174/1871527314666150529144804 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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