A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress
Substance abuse increases an individual's vulnerability to stress-related illnesses, which is presumably mediated by drug-induced neural adaptations that alter subsequent responses to stress. Here, we identify repressive histone methylation in nucleus accumbens (NAc), an important brain reward...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/92331 https://orcid.org/0000-0002-3854-5968 |
| _version_ | 1826208854586687488 |
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| author | Covington III, Herbert E. Maze, Ian Sun, HaoSheng Bomze, Howard M. DeMaio, Kristine D. Wu, Emma Y. Dietz, David M. Lobo, Mary Kay Ghose, Subroto Mouzon, Ezekiel Neve, Rachael L. Tamminga, Carol A. Nestler, Eric J. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Covington III, Herbert E. Maze, Ian Sun, HaoSheng Bomze, Howard M. DeMaio, Kristine D. Wu, Emma Y. Dietz, David M. Lobo, Mary Kay Ghose, Subroto Mouzon, Ezekiel Neve, Rachael L. Tamminga, Carol A. Nestler, Eric J. |
| author_sort | Covington III, Herbert E. |
| collection | MIT |
| description | Substance abuse increases an individual's vulnerability to stress-related illnesses, which is presumably mediated by drug-induced neural adaptations that alter subsequent responses to stress. Here, we identify repressive histone methylation in nucleus accumbens (NAc), an important brain reward region, as a key mechanism linking cocaine exposure to increased stress vulnerability. Repeated cocaine administration prior to subchronic social defeat stress potentiated depressive-like behaviors in mice through decreased levels of histone H3 lysine 9 dimethylation in NAc. Cre-mediated reduction of the histone methyltransferase, G9a, in NAc promoted increased susceptibility to social stress, similar to that observed with repeated cocaine. Conversely, G9a overexpression in NAc after repeated cocaine protected mice from the consequences of subsequent stress. This resilience was mediated, in part, through repression of BDNF-TrkB-CREB signaling, which was induced after repeated cocaine or stress. Identifying such common regulatory mechanisms may aid in the development of new therapies for addiction and depression. |
| first_indexed | 2024-09-23T14:13:41Z |
| format | Article |
| id | mit-1721.1/92331 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:13:41Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/923312022-09-28T19:19:22Z A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress Covington III, Herbert E. Maze, Ian Sun, HaoSheng Bomze, Howard M. DeMaio, Kristine D. Wu, Emma Y. Dietz, David M. Lobo, Mary Kay Ghose, Subroto Mouzon, Ezekiel Neve, Rachael L. Tamminga, Carol A. Nestler, Eric J. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Neve, Rachael L. Substance abuse increases an individual's vulnerability to stress-related illnesses, which is presumably mediated by drug-induced neural adaptations that alter subsequent responses to stress. Here, we identify repressive histone methylation in nucleus accumbens (NAc), an important brain reward region, as a key mechanism linking cocaine exposure to increased stress vulnerability. Repeated cocaine administration prior to subchronic social defeat stress potentiated depressive-like behaviors in mice through decreased levels of histone H3 lysine 9 dimethylation in NAc. Cre-mediated reduction of the histone methyltransferase, G9a, in NAc promoted increased susceptibility to social stress, similar to that observed with repeated cocaine. Conversely, G9a overexpression in NAc after repeated cocaine protected mice from the consequences of subsequent stress. This resilience was mediated, in part, through repression of BDNF-TrkB-CREB signaling, which was induced after repeated cocaine or stress. Identifying such common regulatory mechanisms may aid in the development of new therapies for addiction and depression. 2014-12-16T17:46:28Z 2014-12-16T17:46:28Z 2011-08 Article http://purl.org/eprint/type/JournalArticle 08966273 1097-4199 http://hdl.handle.net/1721.1/92331 Covington, Herbert E., Ian Maze, HaoSheng Sun, Howard M. Bomze, Kristine D. DeMaio, Emma Y. Wu, David M. Dietz, et al. “A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress.” Neuron 71, no. 4 (August 2011): 656–670. © 2011 Elsevier Inc. https://orcid.org/0000-0002-3854-5968 en_US http://dx.doi.org/10.1016/j.neuron.2011.06.007 Neuron Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Covington III, Herbert E. Maze, Ian Sun, HaoSheng Bomze, Howard M. DeMaio, Kristine D. Wu, Emma Y. Dietz, David M. Lobo, Mary Kay Ghose, Subroto Mouzon, Ezekiel Neve, Rachael L. Tamminga, Carol A. Nestler, Eric J. A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress |
| title | A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress |
| title_full | A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress |
| title_fullStr | A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress |
| title_full_unstemmed | A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress |
| title_short | A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress |
| title_sort | role for repressive histone methylation in cocaine induced vulnerability to stress |
| url | http://hdl.handle.net/1721.1/92331 https://orcid.org/0000-0002-3854-5968 |
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