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

Summary: 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 suc...

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Autores principales:	Gui-Ying Zan, Yu-Jun Wang, Xue-Ping Li, Jun-Fan Fang, Song-Yu Yao, Jun-Ying Du, Qian Wang, Xiang Sun, Rui Liu, Xiao-Mei Shao, Jian-Dong Long, Jing-Rui Chai, Ying-Zhi Deng, Ye-Qing Chen, Qing-Lin Li, Jian-Qiao Fang, Zhi-Qiang Liu, Jing-Gen Liu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	dynorphin/κ-opioid receptor glutamate transporter 1 amygdala nucleus accumbens morphine abstinence depression Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/28a139f7693d43c18cec2da3add1381a
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spelling	oai:doaj.org-article:28a139f7693d43c18cec2da3add1381a2021-11-04T04:28:59ZAmygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence2211-124710.1016/j.celrep.2021.109913https://doaj.org/article/28a139f7693d43c18cec2da3add1381a2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013863https://doaj.org/toc/2211-1247Summary: 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 κ-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.Gui-Ying ZanYu-Jun WangXue-Ping LiJun-Fan FangSong-Yu YaoJun-Ying DuQian WangXiang SunRui LiuXiao-Mei ShaoJian-Dong LongJing-Rui ChaiYing-Zhi DengYe-Qing ChenQing-Lin LiJian-Qiao FangZhi-Qiang LiuJing-Gen LiuElsevierarticledynorphin/κ-opioid receptorglutamate transporter 1amygdalanucleus accumbensmorphine abstinencedepressionBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109913- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dynorphin/κ-opioid receptor glutamate transporter 1 amygdala nucleus accumbens morphine abstinence depression Biology (General) QH301-705.5
spellingShingle	dynorphin/κ-opioid receptor glutamate transporter 1 amygdala nucleus accumbens morphine abstinence depression Biology (General) QH301-705.5 Gui-Ying Zan Yu-Jun Wang Xue-Ping Li Jun-Fan Fang Song-Yu Yao Jun-Ying Du Qian Wang Xiang Sun Rui Liu Xiao-Mei Shao Jian-Dong Long Jing-Rui Chai Ying-Zhi Deng Ye-Qing Chen Qing-Lin Li Jian-Qiao Fang Zhi-Qiang Liu Jing-Gen Liu Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence
description	Summary: 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 κ-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.
format	article
author	Gui-Ying Zan Yu-Jun Wang Xue-Ping Li Jun-Fan Fang Song-Yu Yao Jun-Ying Du Qian Wang Xiang Sun Rui Liu Xiao-Mei Shao Jian-Dong Long Jing-Rui Chai Ying-Zhi Deng Ye-Qing Chen Qing-Lin Li Jian-Qiao Fang Zhi-Qiang Liu Jing-Gen Liu
author_facet	Gui-Ying Zan Yu-Jun Wang Xue-Ping Li Jun-Fan Fang Song-Yu Yao Jun-Ying Du Qian Wang Xiang Sun Rui Liu Xiao-Mei Shao Jian-Dong Long Jing-Rui Chai Ying-Zhi Deng Ye-Qing Chen Qing-Lin Li Jian-Qiao Fang Zhi-Qiang Liu Jing-Gen Liu
author_sort	Gui-Ying Zan
title	Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence
title_short	Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence
title_full	Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence
title_fullStr	Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence
title_full_unstemmed	Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence
title_sort	amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/28a139f7693d43c18cec2da3add1381a
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Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence

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