CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits

Deanna L. Wallace, Ming Hu Han, Danielle L. Graham, Thomas A. Green, Vincent Vialou, Sergio D. Ĩiguez, Jun Li Cao, Anne Kirk, Sumana Chakravarty, Arvind Kumar, Vaishnav Krishnan, Rachael L. Neve, Don C. Cooper, Carlos A. Bolãos, Michel Barrot, Colleen A. McClung, Eric J. Nestler

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201 Scopus citations

Abstract

Here, we characterized behavioral abnormalities induced by prolonged social isolation in adult rodents. Social isolation induced both anxiety- and anhedonia-like symptoms and decreased cAMP response element-binding protein (CREB) activity in the nucleus accumbens shell (NAcSh). All of these abnormalities were reversed by chronic, but not acute, antidepressant treatment. However, although the anxiety phenotype and its reversal by antidepressant treatment were CREB-dependent, the anhedonia-like symptoms were not mediated by CREB in NAcSh. We found that decreased CREB activity in NAcSh correlated with increased expression of certain K+ channels and reduced electrical excitability of NAcSh neurons, which was sufficient to induce anxiety-like behaviors and was reversed by chronic antidepressant treatment. Together, our results describe a model that distinguishes anxiety- and depression-like behavioral phenotypes, establish a selective role of decreased CREB activity in NAcSh in anxiety-like behavior, and provide a mechanism by which antidepressant treatment alleviates anxiety symptoms after social isolation.

Original languageEnglish (US)
Pages (from-to)200-209
Number of pages10
JournalNature Neuroscience
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Wallace, D. L., Han, M. H., Graham, D. L., Green, T. A., Vialou, V., Ĩiguez, S. D., Cao, J. L., Kirk, A., Chakravarty, S., Kumar, A., Krishnan, V., Neve, R. L., Cooper, D. C., Bolãos, C. A., Barrot, M., McClung, C. A., & Nestler, E. J. (2009). CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits. Nature Neuroscience, 12(2), 200-209. https://doi.org/10.1038/nn.2257