Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens

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Abstract

Despite abundant expression of DNA methyltransferases (Dnmt’s) in brain, the regulation and behavioral role of DNA methylation remain poorly understood. We find that Dnmt3a expression is regulated in mouse nucleus accumbens (NAc) by chronic cocaine and chronic social defeat stress. Moreover, NAc specific manipulations that block DNA methylation potentiate cocaine reward and exert antidepressant-like effects, whereas NAc specific Dnmt3a overexpression attenuates cocaine reward and is pro-depressant. On a cellular level, we show that chronic cocaine selectively increases thin dendritic spines on NAc neurons and that DNA methylation is both necessary and sufficient to mediate these effects. These data establish the importance of Dnmt3a in the NAc in regulating cellular and behavioral plasticity to emotional stimuli.

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Author and article information

Journal

Journal ID (nlm-journal-id): 9809671

Journal ID (pubmed-jr-id): 21092

Journal ID (nlm-ta): Nat Neurosci

Title: Nature neuroscience

ISSN (Print): 1097-6256

ISSN (Electronic): 1546-1726

Publication date Nihms-submitted: 23 July 2010

Publication date (Electronic): 22 August 2010

Publication date (Print): September 2010

Publication date PMC-release: 1 March 2011

Volume: 13

Issue: 9

Pages: 1137-1143

Affiliations

[1 ]Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY

[2 ]Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX

[3 ]Department of Psychology, Florida State University, Tallahassee, FL

[4 ]Department of Biomedical Sciences, Florida State University, Tallahassee, FL

[5 ]Department of Clinical Sciences, The University of Texas Southwestern Medical Center, Dallas, TX

[6 ]Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA

[7 ]Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

[8 ]Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA

Author notes

[* ]Correspondence and requests for materials should be addressed to E.J.N. ( eric.nestler@ 123456mssm.edu )

Article

Manuscript ID: nihpa223697

DOI: 10.1038/nn.2619

PMC ID: 2928863

PubMed ID: 20729844

SO-VID: 2776f27a-351a-4a0d-a803-aa96378afe27

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