CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits (Nat Neurosci, 2009, doi:10.1038/nm.2257)

報告日期: 2009/05/22
報告時間: 16:00/16:50
報告學生: 張智華
講評老師: 游一龍
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980522-2.pdf

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

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

Nat Neurosci 12, 200 - 209 (2009).

 

Speaker: Chang, Chih-Hua (張智華)

Commentator: Yu, Lung, Ph.D.(游一龍 老師)

Time: 2009.05.22. 16:00 – 16:50

Place: Room 602

 

Abstract

The nucleus accumbens shell (NAcSh) has been proposed to be a key area not only for responses to drugs of abuse but also for the behavioral response to natural rewards, such as food and water intake or sexual behavior. The activity of CREB in the NAcSh has been proved a key regulator of an animal's responses to emotional stimuli. Prolong social isolation of adult rats induces a state of profound anxiety, which is mediated by decreased activity of CREB in the NAcSh. These anxiety symptoms induced by social isolation are blocked by viral-mediated overexpression of CREB in the NAcSh. The present study found that, despite a decrease in CREB activity in the NAcSh, the adulthood social isolation also induced anhedonia (inability to experience pleasure) and that chronic administration of a standard antidepressant medication reversed both the anxiety- and depression-like symptoms, and normalized CREB activity in the NAcSh, seen after social isolation. The anxiety-like symptoms, but not the anhedonia-like symptoms, were directly related to reduced CREB activity in the NAcSh. The authors then used Affymetrix microarray analysis to gain insight into the molecular mechanisms by which social isolation, antidepressants and CREB regulate NAcSh function. The results support a scheme whereby downregulation of CREB activity, induced by social isolation, upregulates several K+ channels and depresses the excitability of NAcSh neurons, which then leads to anxiety-like symptoms.

 

References 1-3

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2. Barrot, M., et al. Regulation of anxiety and initiation of sexual behavior by CREB in the nucleus accumbens. Proc Natl Acad Sci U S A 102, 8357-8362 (2005).

3. Carlezon, W.A., Jr., Duman, R.S. & Nestler, E.J. The many faces of CREB. Trends Neurosci 28, 436-445 (2005).