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Upregulation of dynorphin/kappa opioid receptor system in the dorsal hippocampus contributes to morphine withdrawal-induced place aversion

文献类型：期刊论文

作者Chen, Yan5; Wang, Chen-yao2,3,4; Zan, Gui-ying3,4; Yao, Song-yu1; Deng, Ying-zhi3,4; Shu, Xue-lian2,3,4; Wu, Wei-wei3,4; Ma, Yan3,4; Wang, Yu-jun3,4; Yu, Chang-xi5
刊名ACTA PHARMACOLOGICA SINICA
出版日期2022-09-20
页码8
ISSN号1671-4083
关键词morphine withdrawal conditioned place aversion kappa opioid receptor p38 MAPK norBNI dorsal hippocampus
DOI10.1038/s41401-022-00987-3
通讯作者Wang, Yu-jun(yjwang@simm.ac.cn) ; Yu, Chang-xi(changxiyu@mail.fjmu.edu.cn)
英文摘要Aversive emotion of opioid withdrawal generates motivational state leading to compulsive drug seeking and taking. Kappa opioid receptor (KOR) and its endogenous ligand dynorphin have been shown to participate in the regulation of aversive emotion. In the present study, we investigated the role of dynorphin/KOR system in the aversive emotion following opioid withdrawal in acute morphine-dependent mice. We found that blockade of KORs before pairing by intracerebroventricular injection of KOR antagonist norBNI (20, 40 mu g) attenuated the development of morphine withdrawal-induced conditioned place aversion (CPA) behavior. We further found that morphine withdrawal increased dynorphin A expression in the dorsal hippocampus, but not in the amygdala, prefrontal cortex, nucleus accumbens, and thalamus. Microinjection of norBNI (20 mu g) into the dorsal hippocampus significantly decreased morphine withdrawal-induced CPA behavior. We further found that p38 MAPK was significantly activated in the dorsal hippocampus after morphine withdrawal, and the activation of p38 MAPK was blocked by pretreatment with norBNI. Accordingly, microinjection of p38 MAPK inhibitor SB203580 (5 mu g) into the dorsal hippocampus significantly decreased morphine withdrawal-produced CPA behavior. This study demonstrates that upregulation of dynorphin/KOR system in the dorsal hippocampus plays a critical role in the formation of aversive emotion associated with morphine withdrawal, suggesting that KOR antagonists may have therapeutic value for the treatment of opioid withdrawal-induced mood-related disorders.
WOS关键词DEPRESSIVE-LIKE BEHAVIORS ; PROTEIN-KINASE ACTIVATION ; P38 MAPK ; STRESS ; AMYGDALA ; INVOLVEMENT ; ANTAGONISM ; EXPRESSION ; ADDICTION ; LIGANDS
资助项目Ministry of Science and Technology[2021ZD0203500] ; Ministry of Science and Technology[2021ZD0202900] ; National Natural Science Foundation of China[82030112] ; National Natural Science Foundation of China[81773710] ; Science and Technology Commission of Shanghai Municipality[20ZR1468200] ; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions[NYKFKT2019015]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者NATURE PUBL GROUP
WOS记录号WOS:000855600600001
源URL[http://119.78.100.183/handle/2S10ELR8/302467]  
专题新药研究国家重点实验室
通讯作者Wang, Yu-jun; Yu, Chang-xi
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
2.Univ Chinese Acad Sci, 19 A Yuquan Rd, Beijing 100049, Peoples R China
3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
5.Fujian Med Univ, Sch Pharm, Dept Pharmacol, Fuzhou 350122, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Yan,Wang, Chen-yao,Zan, Gui-ying,et al. Upregulation of dynorphin/kappa opioid receptor system in the dorsal hippocampus contributes to morphine withdrawal-induced place aversion[J]. ACTA PHARMACOLOGICA SINICA,2022:8.
APA Chen, Yan.,Wang, Chen-yao.,Zan, Gui-ying.,Yao, Song-yu.,Deng, Ying-zhi.,...&Liu, Jing-gen.(2022).Upregulation of dynorphin/kappa opioid receptor system in the dorsal hippocampus contributes to morphine withdrawal-induced place aversion.ACTA PHARMACOLOGICA SINICA,8.
MLA Chen, Yan,et al."Upregulation of dynorphin/kappa opioid receptor system in the dorsal hippocampus contributes to morphine withdrawal-induced place aversion".ACTA PHARMACOLOGICA SINICA (2022):8.

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来源：上海药物研究所

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