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/k 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 k 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 k 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 k 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/k opioid receptor system in the amygdala leads to the emergence of depression following chronic social defeat stress,and sheds light on k opioid receptor antagonists as potential therapeutic agents for the prevention and treatment of depression following chronic stress.

Gui-ying Zan;Xiang Sun;Yu-jun Wang;Rui Liu;Chen-yao Wang;Wei-jia Du;Liu-bin Guo;Jing-rui Chai;Qing-lin Li;Zhi-qiang Liu;Jing-gen Liu

Department of Anesthesiology,Shanghai First Maternity and Infant Hospital,Tongji University School of Medicine,Shanghai 201204,China;Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;Key Laboratory of Xin'an Medicine,Ministry of Education,Anhui Province Key Laboratory of R&D of Chinese Medicine,Anhui University of Chinese Medicine,Hefei 230038,China;University of Chinese Academy of Sciences,Beijing 100049,China

中国药理学报（英文版）

[1]Gui-ying Zan;Xiang Sun;Yu-jun Wang;Rui Liu;Chen-yao Wang;Wei-jia Du;Liu-bin Guo;Jing-rui Chai;Qing-lin Li;Zhi-qiang Liu;Jing-gen Liu-.Amygdala dynorphin/K opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress)[J].中国药理学报（英文版）,2022(03):577-587

dynorphin,norBNI

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