Amygdala dynorphin/kappa opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress

doi:10.1038/s41401-021-00677-6

	Amygdala dynorphin/kappa opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress
	Zan, Gui-ying 1,2; Sun, Xiang 3; Wang, Yu-jun 2; Liu, Rui 1; Wang, Chen-yao 2,4; Du, Wei-jia 1; Guo, Liu-bin 2; Chai, Jing-rui 2; Li, Qing-lin 3; Liu, Zhi-qiang 1
刊名	ACTA PHARMACOLOGICA SINICA
	2021-05-25
页码	11
关键词	depression social defeat stress amygdala κ opioid receptor dynorphin c-fos ERK norBNI
ISSN号	1671-4083
DOI	10.1038/s41401-021-00677-6
通讯作者	Li, Qing-lin(qinglin_lee@hotmail.com) ; Liu, Zhi-qiang(drliuzhiqiang@163.com)
英文摘要	Major depression disorder is a severe and recurrent neuropsychological disorder characterized by lowered mood and social activity and cognitive impairment. Owing to unclear molecular mechanisms of depression, limited interventions are available in clinic. In this study we investigated the role of dynorphin/kappa opioid receptor system in the development of depression. Mice were subjected to chronic social defeat stress for 14 days. Chronic social defeat stress induced significant social avoidance in mice characterized by decreased time duration in the interaction zone and increased time duration in the corner zone. Pre-administration of a kappa opioid receptor antagonist norBNI (10 mg/kg, i.p.) could prevent the development of social avoidance induced by chronic social defeat stress. Social avoidance was not observed in kappa opioid receptor knockout mice subjected to chronic social defeat stress. We further revealed that social defeat stress activated c-fos and ERK signaling in the amygdala without affecting the NAc, hippocampus and hypothalamus, and ERK activation was blocked by systemic injection of norBNI. Finally, the expression of dynorphin A, the endogenous ligand of kappa opioid receptor, was significantly increased in the amygdala following social defeat stress; microinjection of norBNI into the amygdala prevented the development of depressive-like behaviors caused by social defeat stress. The present study demonstrates that upregulated dynorphin/kappa opioid receptor system in the amygdala leads to the emergence of depression following chronic social defeat stress, and sheds light on kappa opioid receptor antagonists as potential therapeutic agents for the prevention and treatment of depression following chronic stress.
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[81771188] ; National Natural Science Foundation of China[81773710] ; National Natural Science Foundation of China[81801321] ; Science and Technology Commission of Shanghai Municipality[19401930500] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2017334] ; China Postdoctoral Science Foundation[2018M640423]
WOS关键词	PROTEIN-KINASE-C ; BASOLATERAL AMYGDALA ; SELECTIVE SEROTONIN ; ACTIVATION ; ANXIETY ; BRAIN ; INHIBITION ; EXPRESSION ; GLUTAMATE ; REWARD
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000654149400003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297292]
专题	中国科学院上海药物研究所
通讯作者	Li, Qing-lin; Liu, Zhi-qiang
作者单位	1.Tongji Univ, Shanghai Matern & Infant Hosp 1, Dept Anesthesiol, Sch Med, Shanghai 201204, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Anhui Univ Chinese Med, Key Lab Xinan Med, Anhui Prov Key Lab R&D Chinese Med, Minist Educ, Hefei 230038, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zan, Gui-ying,Sun, Xiang,Wang, Yu-jun,et al. Amygdala dynorphin/kappa opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress[J]. ACTA PHARMACOLOGICA SINICA,2021:11.
APA	Zan, Gui-ying.,Sun, Xiang.,Wang, Yu-jun.,Liu, Rui.,Wang, Chen-yao.,...&Liu, Jing-gen.(2021).Amygdala dynorphin/kappa opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress.ACTA PHARMACOLOGICA SINICA,11.
MLA	Zan, Gui-ying,et al."Amygdala dynorphin/kappa opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress".ACTA PHARMACOLOGICA SINICA (2021):11.