Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence.
Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence.
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杏仁核 γ-阿片受体依赖性上调谷氨酸转运蛋白 1 介导阿片类药物戒断的抑郁样行为。
DOI：
10.1016/j.celrep.2021.109913
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发表时间：
2021-11
期刊：
影响因子：
8.8
通讯作者：
Liu Jing-Gen
中科院分区：
文献类型：
--
作者：
Zan Gui-Ying;Wang Yu-Jun;Li Xue-Ping;Fang Jun-Fan;Yao Song-Yu;Du Jun-Ying;Wang Qian;Sun Xiang;Liu Rui;Shao Xiao-Mei;Long Jian-Dong;Chai Jing-Rui;Deng Ying-Zhi;Chen Ye-Qing;Li Qing-Lin;Fang Jian-Qiao;Liu Zhi-Qiang;Liu Jing-Gen
阿片类药物产生强烈的奖励效应，但戒断阿片类药物使用会产生严重的负面情绪。抑郁症是阿片类药物戒断后最常见的情绪障碍之一，也是阿片类药物复吸的主要原因。然而，这种厌恶情绪处理的神经生物学基础却知之甚少。在这里，我们发现吗啡戒断通过增加杏仁核中内源性KOR配体强啡肽的表达来激活κ-阿片受体（KOR），这反过来又通过激活p38丝裂原活化蛋白激酶（MAPK）来促进谷氨酸转运蛋白1（GLT 1）的表达。GLT 1表达的上调通过调节杏仁核对丘脑腹侧核（NAc）的兴奋性输入而促进阿片类戒断引起的抑郁样行为。杏仁核内注射GLT 1抑制剂DHK或敲低杏仁核中GLT 1表达显著抑制吗啡戒断诱导的抑郁样行为。杏仁核-NAc投射的药理学和药物遗传学激活可防止吗啡戒断诱导的行为。总的来说，我们的研究提供了关键的分子和电路的见解与阿片类药物戒断抑郁症的机制。
Opiates produce a strong rewarding effect, but abstinence from opiate use emerges with severe negative emotions. Depression is one of the most frequent emotion disorders associated with opiate abstinence, which is thought to be a main cause for relapse. However, neurobiological bases of such an aversive emotion processing are poorly understood. Here, we find that morphine abstinence activates κ-opioid receptors (KORs) by increasing endogenous KOR ligand dynorphin expression in the amygdala, which in turn facilitates glutamate transporter 1 (GLT1) expression by activation of p38 mitogen-activated protein kinase (MAPK). Upregulation of GLT1 expression contributes to opiate-abstinence-elicited depressive-like behaviors through modulating amygdalar glutamatergic inputs to the nucleus accumbens (NAc). Intra-amygdala injection of GLT1 inhibitor DHK or knockdown of GLT1 expression in the amygdala significantly suppresses morphine-abstinence-induced depressive-like behaviors. Pharmacological and pharmacogenetic activation of amygdala-NAc projections prevents morphine-abstinence-induced behaviors. Overall, our study provides key molecular and circuit insights into the mechanisms of depression associated with opiate abstinence.
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影响因子：
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作者：
H. Grassmé;P. Jernigan;R. Hoehn;B. Wilker;Matthias Soddemann;M. Edwards;C. Müller;J. Kornhuber;E. Gulbins
通讯作者：
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Beesdo, Katja;Lau, Jennifer Y. F.;Guyer, Amanda E.;McClure-Tone, Erin B.;Monk, Christopher S.;Nelson, Eric E.;Fromm, Stephen J.;Goldwin, Michelle A.;Wittchen, Hans-Ulrich;Leibenluft, Ellen;Erns, Monique;Pine, Daniel S.
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影响因子：
15.9
作者：
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通讯作者：
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影响因子：
4.7
作者：
Gasull-Camos, Julia;Martinez-Torres, Sara;Castane, Anna
通讯作者：
Castane, Anna
DOI：
--
发表时间：
2015
期刊：
--
影响因子：
--
作者：
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通讯作者：
H. Tejeda;Ashley N. Hanks;Liam Scott;C. Mejias-Aponte;Zoë A. Hughes;P. O’Donnell