Article abstract
Nature Neuroscience 12, 200 - 209 (2009)
Published online: 18 January 2009 | doi:10.1038/nn.2257
CREB regulation of nucleus accumbens excitability mediates social isolation–induced behavioral deficits
Deanna L Wallace1,6,7, Ming-Hu Han1,7, Danielle L Graham1,6, Thomas A Green1,6, Vincent Vialou1,2, Sergio D Iñiguez3, Jun-Li Cao1, Anne Kirk1, Sumana Chakravarty1, Arvind Kumar1, Vaishnav Krishnan1, Rachael L Neve4, Don C Cooper1, Carlos A Bolaños3, Michel Barrot5, Colleen A McClung1 & Eric J Nestler1,2
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.
- Departments of Psychiatry and Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9070, USA.
- Fishberg Department of Neuroscience, Mount Sinai School of Medicine, One Gustav L. Levy Place Box 1065, New York, New York 10029, 02115 USA.
- Department of Psychology, Florida State University, 1107 W. Call Street, Tallahassee, Florida 32306-4301, USA.
- Department of Psychiatry, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02178, USA.
- Institut des Neurosciences Cellulaires et Intégratives, UMR7168, CNRS and University Louis Pasteur, 21 Rue Descartes, 67084 Strasbourg, France.
- Present addresses: Helen Willis Neuroscience Institute, University of California Berkeley, 132 Barker Hall, Berkeley, California 94720, USA (D.L.W.), Merck Laboratories, 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA (D.L.G.), and Department of Pharmacology and Toxicology, Virginia Commonwealth University, 1112 East Clay Street, Richmond, Virginia 23298, USA (T.A.G.).
- These authors contributed equally to this work.
Correspondence to: Eric J Nestler1,2 e-mail: eric.nestler@mssm.edu
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