A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress
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Iii-2011-A Role for Repressiv.pdf
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Author(s)
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
Date Issued
August 2011
Journal
Neuron
Publisher
Elsevier
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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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.
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DOI of Published Version
https://doi.org/10.1016/j.neuron.2011.06.007
