CREB regulation of nucleus accumbens excitability mediates social isolation–induced behavioral deficits
- 18 January 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 12 (2), 200-209
- https://doi.org/10.1038/nn.2257
Abstract
CAMP response element–binding protein (CREB) is a key regulator of the nucleus accumbens shell function in animals' responses to emotional stimuli. The present study demonstrates that passive stress in the form of social isolation induces anhedonia and depression-like symptoms that are mediated by CREB activity and neuronal excitability. 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.This publication has 47 references indexed in Scilit:
- Cytoplasmic BK Ca channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neuronsProceedings of the National Academy of Sciences of the United States of America, 2008
- Sexual behavior in male rodentsHormones and Behavior, 2007
- Epigenetic regulation in psychiatric disordersNature Reviews Neuroscience, 2007
- Depression-Like Behavior and Stressor-Induced Neuroendocrine Activation in Female Prairie Voles Exposed to Chronic Social IsolationPsychosomatic Medicine, 2007
- Serotonin and the neurobiology of the ejaculatory thresholdNeuroscience & Biobehavioral Reviews, 2006
- Sexual experience in female rodents: Cellular mechanisms and functional consequencesBrain Research, 2006
- High-conductance potassium channels of the SLO familyNature Reviews Neuroscience, 2006
- Social isolation delays the positive effects of running on adult neurogenesisNature Neuroscience, 2006
- The many faces of CREBTrends in Neurosciences, 2005
- The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addictionPharmacology & Therapeutics, 2004