Opposing actions of chronic stress and chronic nicotine on striatal function in mice
Opposing actions of chronic stress and chronic nicotine on striatal function in mice
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DOI：
10.1016/j.neulet.2008.05.038
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发表时间：
2008-07-25
影响因子：
2.5
通讯作者：
De Biasi, Mariella
中科院分区：
文献类型：
--
作者：
Salas, Ramiro;De Biasi, Mariella
压力是毒瘾发展和复发的主要危险因素。事实上，所有滥用药物都是通过增加纹状体细胞外多巴胺水平来起作用的。为了了解压力和药物暴露之间的相互作用，我们研究了同时长期尼古丁和慢性压力暴露对小鼠纹状体多巴胺水平的影响。 C57BI6/J 小鼠接受饮用水或对照溶液中的尼古丁治疗至少 6 周。一些小鼠因每天暴露在寒冷、摇晃或束缚中而长期承受压力。接受尼古丁治疗的小鼠的几个大脑区域显示皮巴替丁结合上调。在接受慢性尼古丁和应激治疗的小鼠中，除背侧纹状体外的所有研究区域中的皮巴替丁结合均增加。因此，微透析用于测量长期接受尼古丁、压力或两者同时治疗的小鼠背侧纹状体的细胞外多巴胺水平。为了测量纹状体对不同挑战的反应，我们在急性注射盐水、尼古丁和可卡因后进行了微透析。慢性尼古丁增强了尼古丁依赖性多巴胺的释放，而慢性压力则减弱了对可卡因的反应。当小鼠同时受到慢性尼古丁和慢性应激时，尼古丁和可卡因依赖性多巴胺的释放与对照动物没有区别。总之，我们的数据表明，慢性压力和慢性尼古丁相互抵消了纹状体多巴胺释放的影响。这种效应可能是通过烟碱乙酰胆碱受体上调的变化介导的。当尼古丁和压力同时存在时，纹状体功能的“正常化”可能有助于解释压力相关疾病和药物滥用之间的共病。 Crown 版权所有 (C) 2008 由 Elsevier Ireland Ltd 出版。保留所有权利。
Stress is a major risk factor in drug addiction development and relapse. Virtually all drugs of abuse act by increasing extracellular dopamine levels in the striatum. To gain an understanding of the interaction between stress and drug exposure, we studied the effects of concomitant chronic nicotine and chronic stress exposure on mouse striatal dopamine levels. C57BI6/J mice were treated with nicotine in the drinking water or control solution for at least 6 weeks. Some mice were chronically stressed by daily exposure to cold, shaking or restrain. Nicotine-treated mice showed up-regulation of epibatidine binding in several brain regions. In mice treated with both chronic nicotine and stress, epibatidine binding was increased in all studied areas except the dorsal striatum. Therefore, microdialysis was used to measure extracellular dopamine levels in the dorsal striatum of mice chronically treated with nicotine, stress, or both. To have a measure of striatal response to different challenges, we performed microdialysis after acute injection of saline, nicotine, and cocaine. Chronic nicotine enhanced nicotine-dependent dopamine release, while chronic stress blunted the response to cocaine. When mice were subjected to both chronic nicotine and chronic stress, nicotine- and cocaine-dependent dopamine release was undistinguishable from that of control animals. In conclusion, our data suggest that chronic stress and chronic nicotine counteract each other's effect on dopamine release in the striatum. This effect might be mediated by changes in nicotinic acetylcholine receptor up-regulation. This "normalization" of striatal function when both nicotine and stress are present might help explain the comorbidity between stress-related disorders and drug abuse. Crown Copyright (C) 2008 Published by Elsevier Ireland Ltd. All rights reserved.