CORTICOTROPIN-RELEASING FACTOR IN THE NUCLEUS ACCUMBENS SHELL INDUCES SWIM DEPRESSION, ANXIETY, AND ANHEDONIA ALONG WITH CHANGES IN LOCAL DOPAMINE/ACETYLCHOLINE BALANCE
CORTICOTROPIN-RELEASING FACTOR IN THE NUCLEUS ACCUMBENS SHELL INDUCES SWIM DEPRESSION, ANXIETY, AND ANHEDONIA ALONG WITH CHANGES IN LOCAL DOPAMINE/ACETYLCHOLINE BALANCE
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DOI：
10.1016/j.neuroscience.2011.12.009
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发表时间：
2012-03-29
期刊：
影响因子：
3.3
通讯作者：
Hoebel, B. G.
中科院分区：
文献类型：
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作者：
Chen, Y. -W.;Rada, P. V.;Hoebel, B. G.
神经核壳（NAcS）通过促肾上腺皮质激素释放因子（CRF）参与控制应激反应。除了研究表明NAcS中的CRF增加食欲动机外，还有间接证据表明NAcS CRF也可能引起厌恶反应，这些行为可能通过局部多巴胺（DA）和乙酰胆碱（ACh）系统介导。为了提供对该假设的直接检验，我们使用了针对NAcS植入套管的雄性Sprague-Dawley大鼠。实验1显示局部注射CRF（10或50 ng/侧）可增加强迫游泳试验中的不动性，并且CRF拮抗剂D-Phe-CRF（（12-41））可减轻这种抑郁样行为。在实验2中，注射CRF（250 ng/侧）也降低了大鼠对蔗糖的偏好，而在实验3中，CRF（50或250 ng/侧）诱导了大鼠在高架十字迷宫和旷场中的焦虑样行为。实验4中相同剂量的CRF未能改变大鼠的自发活动，表明这些行为变化不是由活动缺陷引起的。在实验5中，从体内微透析的结果显示，CRF在NAcS显着增加当地的细胞外ACh，同时也产生了一个小的增加DA。这些结果表明，NAcS CRF可以产生各种厌恶的行为，包括游泳抑郁症，快感缺乏症，焦虑，除了接近行为。他们认为，这些行为可能部分是通过增强NAcS中ACh和DA的激活而发生的，这支持了该脑区在介导压力双重效应中的作用。(C)2012年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The nucleus accumbens shell (NAcS) has been implicated in controlling stress responses through corticotropin-releasing factor (CRF). In addition to studies indicating that CRF in the NAcS increases appetitive motivation, there is indirect evidence suggesting that NAcS CRF may also cause aversive responses and that these behaviors may be mediated through local dopamine (DA) and acetylcholine (ACh) systems. To provide a direct test of this hypothesis, we used male Sprague-Dawley rats with implanted cannulas aimed at the NAcS. Experiment 1 showed local CRF injection (10 or 50 ng/side) to increase immobility in the forced swim test and a CRF antagonist D-Phe-CRF ((12-41)) to attenuate this depressive-like behavior. In Experiment 2, injection of CRF (250 ng/side) also decreased the rats' preference for sucrose, while in Experiment 3, CRF (50 or 250 ng/side) induced anxiety-like behaviors in an elevated plus maze and open field. These same doses of CRF in Experiment 4 failed to alter the rats' locomotor activity, indicating that these behavioral changes were not caused by deficits in activity. In Experiment 5, results from in vivo microdialysis revealed that CRF in the NAcS markedly increased local extracellular ACh, while also producing a small increase in DA. These results show that NAcS CRF can generate a variety of aversive behaviors, including swim depression, anhedonia, and anxiety, in addition to approach behavior. They suggest that these behaviors may occur, in part, through enhanced activation of ACh and DA in the NAcS, respectively, supporting a role for this brain area in mediating the dual effects of stress. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.