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Amygdalar k-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence

文献类型：期刊论文

作者Zan, Gui-Ying1,2; Wang, Yu-Jun1; Li, Xue-Ping1,3; Fang, Jun-Fan4; Yao, Song-Yu5; Du, Jun-Ying4; Wang, Qian1; Sun, Xiang6; Liu, Rui2; Shao, Xiao-Mei4
刊名CELL REPORTS
出版日期2021-11-02
卷号37期号:5页码:21
ISSN号2211-1247
DOI10.1016/j.celrep.2021.109913
通讯作者Wang, Yu-Jun(yjwang@simm.ac.cn) ; Fang, Jian-Qiao(fangjiandiao7532@163.com) ; Liu, Zhi-Qiang(drliuzhiqiang@163.com) ; Liu, Jing-Gen(jgliu@simm.ac.cn)
英文摘要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 k-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.
WOS关键词NUCLEUS-ACCUMBENS ; BASOLATERAL AMYGDALA ; DOPAMINE EFFLUX ; P38 MAPK ; SEEKING BEHAVIOR ; MESSENGER-RNA ; REWARD ; STRESS ; ACTIVATION ; EXPRESSION
资助项目National Natural Science Foundation of China[81130087] ; National Natural Science Foundation of China[81671322] ; National Natural Science Foundation of China[82030112] ; National Natural Science Foundation of China[81773710] ; National Natural Science Foundation of China[81771188] ; National Natural Science Foundation of China[81801321] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2017334] ; China Postdoctoral Science Foundation[2018M640423]
WOS研究方向Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000715939600001
源URL[http://119.78.100.183/handle/2S10ELR8/298674]  
专题中国科学院上海药物研究所
通讯作者Wang, Yu-Jun; Fang, Jian-Qiao; Liu, Zhi-Qiang; Liu, Jing-Gen
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China
2.Tongji Univ, Shanghai First Matern & Infant Hosp, Sch Med, Dept Anesthesiol, Shanghai 200092, Peoples R China
3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
4.Zhejiang Chinese Med Univ, Clin Med Coll 3, Key Lab Acupuncture & Neurobiol Zhejiang Prov, Dept Neurobiol & Acupuncture Res, Hangzhou 310053, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
6.Anhui Univ Tradit Chinese Med, Key Lab Xinan Med, Anhui Prov Key Lab R&D Chinese Med, Minist Educ, Hefei 230038, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Zan, Gui-Ying,Wang, Yu-Jun,Li, Xue-Ping,et al. Amygdalar k-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence[J]. CELL REPORTS,2021,37(5):21.
APA Zan, Gui-Ying.,Wang, Yu-Jun.,Li, Xue-Ping.,Fang, Jun-Fan.,Yao, Song-Yu.,...&Liu, Jing-Gen.(2021).Amygdalar k-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence.CELL REPORTS,37(5),21.
MLA Zan, Gui-Ying,et al."Amygdalar k-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence".CELL REPORTS 37.5(2021):21.

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来源：上海药物研究所

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