Amygdala dynorphin/κ opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress
Amygdala dynorphin/κ opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress
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杏仁核强啡肽/卡帕阿片受体系统调节小鼠慢性社交失败压力后的抑郁样行为
DOI：
10.1038/s41401-021-00677-6
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Jing-Gen Liu
中科院分区：
文献类型：
--
作者：
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
重度抑郁症是一种严重且易复发的神经精神障碍，其特征为情绪低落、社交活动减少以及认知功能受损。由于抑郁症的分子机制尚不明确，临床上可用的干预措施有限。
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/κ 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 κ 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 κ 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 κ 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/κ opioid receptor system in the amygdala leads to the emergence of depression following chronic social defeat stress, and sheds light on κ opioid receptor antagonists as potential therapeutic agents for the prevention and treatment of depression following chronic stress.
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影响因子：
168.9
作者：
Kupfer, David J.;Frank, Ellen;Phillips, Mary L.
通讯作者：
Phillips, Mary L.
重复的游泳应力诱导阿片类阿片类药物介导的细胞外信号调节激酶1/2的激活。
影响因子：
1.7
作者：
Bruchas MR;Xu M;Chavkin C
通讯作者：
Chavkin C
DOI：
--
发表时间：
2007
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
M. Bruchas;Benjamin B. Land;Megumi Aita;Mei Xu;Sabiha K. Barot;Shuang Li;C. Chavkin
通讯作者：
M. Bruchas;Benjamin B. Land;Megumi Aita;Mei Xu;Sabiha K. Barot;Shuang Li;C. Chavkin
影响因子：
13.5
作者：
Carlezon WA Jr;Béguin C;Knoll AT;Cohen BM
通讯作者：
Cohen BM
影响因子：
15.9
作者：
Lutz PE;Kieffer BL
通讯作者：
Kieffer BL