CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits.
CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits.
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DOI：
10.1038/nn.2257
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发表时间：
2009-02
影响因子：
25
通讯作者：
Nestler, Eric J.
中科院分区：
文献类型：
--
作者：
Wallace, Deanna L.;Han, Ming-Hu;Graham, Danielle L.;Green, Thomas A.;Vialou, Vincent;Iniguez, Sergio D.;Cao, Jun-Li;Kirk, Anne;Chakravarty, Sumana;Kumar, Arvind;Krishnan, Vaishnav;Neve, Rachael L.;Cooper, Don C.;Bolanos, Carlos A.;Barrot, Michel;McClung, Colleen A.;Nestler, Eric J.
在这里，我们描述了成年啮齿动物因长期社会隔离而引起的行为异常。社会隔离会引起焦虑和快感缺失样症状，并降低伏隔核壳 (NAcSh) 中 cAMP 反应元件结合蛋白 (CREB) 的活性。所有这些异常都可以通过慢性而非急性抗抑郁治疗得到逆转。然而，尽管焦虑表型及其通过抗抑郁治疗的逆转是 CREB 依赖性的，但 NAcSh 中的快感缺乏样症状并不是由 CREB 介导的。我们发现 NAcSh 中 CREB 活性的降低与某些 K+ 通道表达的增加和 NAcSh 神经元电兴奋性的降低相关，这足以诱发焦虑样行为，并可以通过长期抗抑郁治疗来逆转。总之，我们的结果描述了一个区分焦虑和抑郁样行为表型的模型，建立了 NAcSh 中 CREB 活性降低在焦虑样行为中的选择性作用，并提供了抗抑郁治疗减轻社会隔离后焦虑症状的机制。
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.
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DOI：
10.1073/pnas.172091899
发表时间：
2002-08-20
影响因子：
11.1
作者：
Barrot, M;Olivier, JDA;Nestler, EJ
通讯作者：
Nestler, EJ
影响因子：
10.6
作者：
Chen, ACH;Shirayama, Y;Duman, RS
通讯作者：
Duman, RS
影响因子：
3.8
作者：
Costello, J;Kendrick, K
通讯作者：
Kendrick, K
影响因子：
2.9
作者：
GRECO, AM;GAMBARDELLA, P;DEFRANCISCIS, P
通讯作者：
DEFRANCISCIS, P
影响因子：
56.9
作者：
Carlezon, WA;Thome, J;Nestler, EJ
通讯作者：
Nestler, EJ