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Epigenetic Landscape of Methamphetamine Use Disorder

The persistence of the addiction phenotype in methamphetamine use disorder (MUD) suggests the potential presence of epigenetic changes and potential structural adaptations that may drive the manifestations of MUD in humans. In the present review, we discuss the evidence that documents the fact that...

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Autores principales: Cadet, Jean Lud, Jayanthi, Subramaniam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185771/
https://www.ncbi.nlm.nih.gov/pubmed/34030618
http://dx.doi.org/10.2174/1570159X19666210524111915
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author Cadet, Jean Lud
Jayanthi, Subramaniam
author_facet Cadet, Jean Lud
Jayanthi, Subramaniam
author_sort Cadet, Jean Lud
collection PubMed
description The persistence of the addiction phenotype in methamphetamine use disorder (MUD) suggests the potential presence of epigenetic changes and potential structural adaptations that may drive the manifestations of MUD in humans. In the present review, we discuss the evidence that documents the fact that methamphetamine exposure can cause changes in epigenetic modifications, including histone acetylation and methylation, as well as DNA methylation and hydroxymethylation in a complex manner that need to be fully dissected. Nevertheless, our work has demonstrated the existence of correlations between behavioral changes and epigenetic alterations during methamphetamine self-administration. We found that prolonged methamphetamine self-administration and contingent footshocks resulted in rats with compulsive drug-taking and abstinent phenotypes. In addition, rats that reduce their methamphetamine intake in the presence of punishment showed increased DNA hydroxymethylation in genes encoding potassium channels in their nucleus accumbens. Moreover, altered DNA hydroxymethylation in those genes led to an increase in their mRNA expression. Additional studies revealed decreased mRNA expression of histone deacetylases associated with increased histone acetylation and induced gene expression in the dorsal striatum. These changes were associated with a reduction in methamphetamine intake in response to contingent footshocks. More research is necessary in order to further dissect how pharmacological or genetic manipulations of identified epigenetic alterations and expression of potassium channels can impact methamphetamine-taking behaviors or relapse to methamphetamine-taking after long periods of abstinence. Investigations that use discovery approaches, such as whole-genome sequencing after chromatin immunoprecipitation, should accelerate our efforts to develop epigenetic therapeutic approaches against MUD.
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spelling pubmed-91857712022-06-28 Epigenetic Landscape of Methamphetamine Use Disorder Cadet, Jean Lud Jayanthi, Subramaniam Curr Neuropharmacol Article The persistence of the addiction phenotype in methamphetamine use disorder (MUD) suggests the potential presence of epigenetic changes and potential structural adaptations that may drive the manifestations of MUD in humans. In the present review, we discuss the evidence that documents the fact that methamphetamine exposure can cause changes in epigenetic modifications, including histone acetylation and methylation, as well as DNA methylation and hydroxymethylation in a complex manner that need to be fully dissected. Nevertheless, our work has demonstrated the existence of correlations between behavioral changes and epigenetic alterations during methamphetamine self-administration. We found that prolonged methamphetamine self-administration and contingent footshocks resulted in rats with compulsive drug-taking and abstinent phenotypes. In addition, rats that reduce their methamphetamine intake in the presence of punishment showed increased DNA hydroxymethylation in genes encoding potassium channels in their nucleus accumbens. Moreover, altered DNA hydroxymethylation in those genes led to an increase in their mRNA expression. Additional studies revealed decreased mRNA expression of histone deacetylases associated with increased histone acetylation and induced gene expression in the dorsal striatum. These changes were associated with a reduction in methamphetamine intake in response to contingent footshocks. More research is necessary in order to further dissect how pharmacological or genetic manipulations of identified epigenetic alterations and expression of potassium channels can impact methamphetamine-taking behaviors or relapse to methamphetamine-taking after long periods of abstinence. Investigations that use discovery approaches, such as whole-genome sequencing after chromatin immunoprecipitation, should accelerate our efforts to develop epigenetic therapeutic approaches against MUD. Bentham Science Publishers 2021-12-13 2021-12-13 /pmc/articles/PMC9185771/ /pubmed/34030618 http://dx.doi.org/10.2174/1570159X19666210524111915 Text en © 2021 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Cadet, Jean Lud
Jayanthi, Subramaniam
Epigenetic Landscape of Methamphetamine Use Disorder
title Epigenetic Landscape of Methamphetamine Use Disorder
title_full Epigenetic Landscape of Methamphetamine Use Disorder
title_fullStr Epigenetic Landscape of Methamphetamine Use Disorder
title_full_unstemmed Epigenetic Landscape of Methamphetamine Use Disorder
title_short Epigenetic Landscape of Methamphetamine Use Disorder
title_sort epigenetic landscape of methamphetamine use disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185771/
https://www.ncbi.nlm.nih.gov/pubmed/34030618
http://dx.doi.org/10.2174/1570159X19666210524111915
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