Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens
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Open Access
- 22 August 2010
- journal article
- research article
- Published by Springer Nature in Nature Neuroscience
- Vol. 13 (9) , 1137-1143
- https://doi.org/10.1038/nn.2619
Abstract
The authors find that the expression of the DNA methyltransferase Dnmt3a in mice is regulated by chronic cocaine and chronic social defeat stress in the nucleus accumbens. Manipulations that block DNA methylation potentiate cocaine reward and cause an antidepressant-like effect. Despite abundant expression of DNA methyltransferases (Dnmts) in brain, the regulation and behavioral role of DNA methylation remain poorly understood. We found that Dnmt3a expression was regulated in mouse nucleus accumbens (NAc) by chronic cocaine use and chronic social defeat stress. Moreover, NAc-specific manipulations that block DNA methylation potentiated cocaine reward and exerted antidepressant-like effects, whereas NAc-specific Dnmt3a overexpression attenuated cocaine reward and was pro-depressant. On a cellular level, we found that chronic cocaine use selectively increased thin dendritic spines on NAc neurons and that DNA methylation was 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.Keywords
This publication has 49 references indexed in Scilit:
- The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbensTrends in Neurosciences, 2010
- The induction of behavioural sensitization is associated with cocaine‐induced structural plasticity in the core (but not shell) of the nucleus accumbensEuropean Journal of Neuroscience, 2004
- Time-Dependent Increases in Brain-Derived Neurotrophic Factor Protein Levels within the Mesolimbic Dopamine System after Withdrawal from Cocaine: Implications for Incubation of Cocaine CravingJournal of Neuroscience, 2003
- Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5Neuroscience, 2003
- Sex Differences in the Behavioral Response to Spatial and Object Novelty in Adult C57BL/6 Mice.Behavioral Neuroscience, 2003
- CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuliProceedings of the National Academy of Sciences, 2002
- Overexpression of 5-HT1B Receptor in Dorsal Raphe Nucleus Using Herpes Simplex Virus Gene Transfer Increases Anxiety Behavior after Inescapable StressJournal of Neuroscience, 2002
- Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaineEuropean Journal of Neuroscience, 1999
- Toxicity of 5-aza-2'-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation.Proceedings of the National Academy of Sciences, 1994
- Depression: a new animal model sensitive to antidepressant treatmentsNature, 1977