Glucocorticoid receptor deletion from the dorsal raphé nucleus of mice reduces dysphoria-like behavior and impairs hypothalamic-pituitary-adrenocortical axis feedback inhibition.
Glucocorticoid receptor deletion from the dorsal raphé nucleus of mice reduces dysphoria-like behavior and impairs hypothalamic-pituitary-adrenocortical axis feedback inhibition.
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DOI：
10.1111/ejn.12538
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Jacobson L
中科院分区：
文献类型：
--
作者：
Vincent MY;Jacobson L
糖皮质激素会导致抑郁和焦虑。糖皮质激素对情绪的作用机制在很大程度上是不明确的。脑背核（DRN）产生大脑中的大部分血清素，并表达糖皮质激素受体（GR）。由于我们之前的研究表明，用于治疗抑郁和焦虑的抗抑郁药会降低DRN GR的表达，我们假设删除DRN GR将具有抗焦虑和抗抑郁的类似作用。我们还假设DRN GR缺失会解除对下丘脑-垂体-肾上腺轴（HPA）活性的抑制。将表达Cre重组酶（DRNGRKO小鼠）或GFP （DRN-GFP小鼠）的腺相关病毒伪型AAV2/9注射到固定GR小鼠的DRN中以验证这些假设。注射后3周，小鼠进行了10天的社会失败或控制处理，并测试了焦虑样行为（开放场测试、升高加迷宫测试）、抑郁样行为（蔗糖偏好、强迫游泳测试（FST）、悬尾测试（TST））、社会互动以及昼夜节律和应激诱导的HPA活性。DRN GR缺失减少了对照组小鼠的焦虑样行为，但在失败小鼠中没有。DRN GR缺失降低了对照组和失败小鼠的FST，并倾向于减少TST绝望样行为，但不影响蔗糖偏好。DRNGRKO小鼠对社会（一种新的小鼠）和中性目标（一个空盒子）的探索增加，这表明DRNGR缺失也促进了主动应对。DRN GR缺失增加了应激调节的HPA活性，但没有强烈改变昼夜HPA活性。我们发现DRN GR在急性应激中介导焦虑和绝望样行为以及调节HPA负反馈的新作用。
Glucocorticoids can cause depression and anxiety. Mechanisms for glucocorticoid effects on mood are largely undefined. The dorsal raphé nucleus (DRN) produces the majority of serotonin in the brain, and expresses glucocorticoid receptors (GR). Since we previously showed that antidepressants used to treat depression and anxiety decrease DRN GR expression, we hypothesized that deleting DRN GR would have anxiolytic- and antidepressant-like effects. We also hypothesized that DRN GR deletion would disinhibit activity of the hypothalamic pituitary adrenal (HPA) axis. Adeno-associated virus pseudotype AAV2/9 expressing either Cre recombinase (DRNGRKO mice) or GFP (DRN-GFP mice) was injected into the DRN of floxed GR mice to test these hypotheses. Three weeks after injection, mice underwent 10d of social defeat or control handling and tested for anxiety-like behavior (open field test, elevated plus maze), depression-like behavior (sucrose preference, forced swim test (FST), tail suspension (TST)), social interaction, and circadian and stress-induced HPA activity. DRN GR deletion decreased anxiety-like behavior in control but not in defeated mice. DRN GR deletion decreased FST and tended to decrease TST despair-like behavior in both control and defeated mice, but did not affect sucrose preference. Exploration of social (a novel mouse) as well as neutral targets (an empty box) was increased in DRNGRKO mice, suggesting that DRN GR deletion also promotes active coping. DRN GR deletion increased stress-regulated HPA activity without strongly altering circadian HPA activity. We have shown a novel role for DRN GR to mediate anxiety- and despair-like behavior and to regulate HPA negative feedback during acute stress.
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影响因子：
4.1
作者：
HERMAN, JP;ADAMS, D;PREWITT, C
通讯作者：
PREWITT, C
影响因子：
10.5
作者：
COOKSON, JC;SILVERSTONE, T;BESSER, GM
通讯作者：
BESSER, GM
DOI：
10.1196/annals.1296.005
发表时间：
2004-01-01
期刊：
STRESS: CURRENT NEUROENDOCRINE AND GENETIC APPROACHES
影响因子：
--
作者：
Abrams, JK;Johnson, PL;Lowry, CA
通讯作者：
Lowry, CA
影响因子：
5.3
作者：
Blugeot, Aurelie;Rivat, Cyril;Becker, Chrystel
通讯作者：
Becker, Chrystel
大脑奖励回路中的中脑边缘多巴胺神经元介导对社交失败和抗抑郁作用的敏感性
DOI：
10.1523/jneurosci.3177-10.2010
发表时间：
2010-12-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cao JL;Covington HE 3rd;Friedman AK;Wilkinson MB;Walsh JJ;Cooper DC;Nestler EJ;Han MH
通讯作者：
Han MH