研究人員發(fā)現(xiàn),，長(zhǎng)期處于社交孤獨(dú)的嚙齒動(dòng)物會(huì)表現(xiàn)出焦慮癥狀，對(duì)快樂(lè)的事情沒(méi)有感覺(jué),，這一最新的研究成果發(fā)表在2009年1月18日在線出版的《自然—神經(jīng)科學(xué)》（Nature Neuroscience）上,。他們的研究顯示，抗抑郁藥物能夠治療或改善與抑郁相關(guān)的焦慮癥狀,。
美國(guó)得克薩斯大學(xué)西南醫(yī)學(xué)中心的Eric Nestler和同事發(fā)現(xiàn),，被圈養(yǎng)在籠子里、社交活動(dòng)隔離的老鼠和小鼠均表現(xiàn)出抑郁癥狀的焦慮行為,，比如不正常的性行為,、對(duì)糖水的興趣減少。他們還發(fā)現(xiàn),，這種長(zhǎng)期的緊張狀態(tài)減少了伏隔核殼中一種CREB蛋白質(zhì)的活性,，伏隔核殼是大腦區(qū)域中負(fù)責(zé)動(dòng)機(jī)和情緒刺激的區(qū)域。長(zhǎng)期用三環(huán)類抗抑郁藥物能夠逆轉(zhuǎn)這些焦慮行為,，并將CREB蛋白質(zhì)恢復(fù)到正常水平,。
這項(xiàng)研究不僅提供了一個(gè)長(zhǎng)期社交隔離的抑郁癥動(dòng)物模式，而且也提供了抗抑郁治療緩解焦慮癥狀的一種新機(jī)制,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Neuroscience,，doi:10.1038/nn.2257，Deanna L Wallace，Eric J Nestler
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 I?iguez3, Jun-Li Cao1, Anne Kirk1, Sumana Chakravarty1, Arvind Kumar1, Vaishnav Krishnan1, Rachael L Neve4, Don C Cooper1, Carlos A Bola?os3, 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.
1 Departments of Psychiatry and Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9070, USA.
2 Fishberg Department of Neuroscience, Mount Sinai School of Medicine, One Gustav L. Levy Place Box 1065, New York, New York 10029, 02115 USA.
3 Department of Psychology, Florida State University, 1107 W. Call Street, Tallahassee, Florida 32306-4301, USA.
4 Department of Psychiatry, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02178, USA.
5 Institut des Neurosciences Cellulaires et Intégratives, UMR7168, CNRS and University Louis Pasteur, 21 Rue Descartes, 67084 Strasbourg, France.
6 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.).
7 These authors contributed equally to this work.
