title: CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits.
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.
authors.affiliation: Department of Psychiatry and Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9070, USA.
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Wallace
authors.forename: Ming-Hu
authors.initials: MH
authors.lastname: Han
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Graham
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Green
authors.forename: Vincent
authors.initials: V
authors.lastname: Vialou
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Iñiguez
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Cao
authors.forename: Anne
authors.initials: A
authors.lastname: Kirk
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
authors.forename: Vaishnav
authors.initials: V
authors.lastname: Krishnan
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Neve
authors.forename: Don C
authors.initials: DC
authors.lastname: Cooper
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bolaños
authors.forename: Michel
authors.initials: M
authors.lastname: Barrot
authors.forename: Colleen A
authors.initials: CA
authors.lastname: McClung
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000342:Affective Symptoms / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D050882:CREB-Binding Protein / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D007099:Imipramine / Q000494:pharmacology; D007763:Lac Operon; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009714:Nucleus Accumbens / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology; D012934:Social Isolation
chemical_list: D018759:Adrenergic Uptake Inhibitors; D015221:Potassium Channels; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; C494365:Crebbp protein, rat; D007099:Imipramine