研究人员发现，长期处于社交孤独的啮齿动物会表现出焦虑症状，对快乐的事情没有感觉，这一最新的研究成果发表在2009年1月18日在线出版的《自然—神经科学》（Nature Neuroscience）上。他们的研究显示，抗抑郁药物能够治疗或改善与抑郁相关的焦虑症状。
美国得克萨斯大学西南医学中心的Eric Nestler和同事发现，被圈养在笼子里、社交活动隔离的老鼠和小鼠均表现出抑郁症状的焦虑行为，比如不正常的性行为、对糖水的兴趣减少。他们还发现，这种长期的紧张状态减少了伏隔核壳中一种CREB蛋白质的活性，伏隔核壳是大脑区域中负责动机和情绪刺激的区域。长期用三环类抗抑郁药物能够逆转这些焦虑行为，并将CREB蛋白质恢复到正常水平。
这项研究不仅提供了一个长期社交隔离的抑郁症动物模式，而且也提供了抗抑郁治疗缓解焦虑症状的一种新机制。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
