CREB regulation of nucleus accumbens excitability mediates social isolation–induced behavioral deficits
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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.
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Normalization of K+ channel function contributes to antidepressant responses in the adult social isolation paradigm.
“while normalization of K± channel function contributes to antidepressant responses49”
From Neurobiology of resilience (2012) · cites this paper as [49]
Prolonged social isolation of adult mice or rats induces depression- and anxiety-like behavioral abnormalities and promotes susceptibility to chronic social defeat stress.
“which induces depression– and anxiety–like behavioral abnormalities49 and promotes susceptibility to chronic social defeat stress71”
From Neurobiology of resilience (2012) · cites this paper as [49]
Induction of particular K+ channel subunits in the nucleus accumbens in response to adult social isolation contributes to depression-like symptoms in this paradigm.
“Induction of particular K+ channel subunits in NAc in response to adult social isolation was shown to contribute to depression–like symptoms seen in this paradigm”
From Neurobiology of resilience (2012) · cites this paper as [49]
K+ channel-mediated adaptations have been observed in the nucleus accumbens after prolonged social isolation of adult mice or rats.
“K+ channel–mediated adaptations have also been observed in NAc after prolonged social isolation of adult mice or rats”
From Neurobiology of resilience (2012) · cites this paper as [49]
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- Authors
- Wallace, D. L., Han, M.-H., Graham, D. L., Green, T. A., Vialou, V., Iñiguez, S. D., Cao, J.-L., Kirk, A., Chakravarty, S., Kumar, A., Krishnan, V., Neve, R. L., Cooper, D. C., Bolaños, C. A., Barrot, M., McClung, C. A., & Nestler, E. J.
- Affiliations
- Virginia Commonwealth University (US)
- The University of Texas Southwestern Medical Center (US)
- Florida State University (US)
- Harvard University (US)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Nestler, Eric J
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2009-01-18
- Volume
- 12
- Issue
- 2
- Pages
- 200-209
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2721778
- OpenAlex
- W2114600491
- Cited by
- 342
- References
- 54
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 17 · 2023: 15 · 2022: 25 · 2021: 25 · 2020: 20 · 2019: 18 · 2018: 17 · 2017: 19 · 2016: 21 · 2015: 17 · 2014: 27 · 2013: 17 · 2012: 29
- FWCI
- 19.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH051399, P50MH066172)
- National Institute on Drug Abuse (K01DA017750, P01DA008227)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- CREB, nucleus accumbens shell, social isolation, anhedonia, anxiety-like behavior, depression-like behavior, neuronal excitability, potassium channels, chronic antidepressant treatment, passive stress, emotional behavior
- MeSH terms
- Affective Symptoms, Animals, Anxiety, Behavior, Animal, Female, Imipramine, Lac Operon, Male, Mice, Transgenic, Nucleus Accumbens, Sexual Behavior, Animal, Social Isolation, Potassium Channels, Rats, Sprague-Dawley, Adrenergic Uptake Inhibitors, Gene Expression Profiling, CREB-Binding Protein, Mice, Rats
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