Dorsal hippocampal NMDA receptor blockade impairs extinction of naloxone-precipitated conditioned place aversion in acute morphine-treated rats by suppressing ERK and CREB phosphorylation in the basolateral amygdala

doi:10.1111/bph.12671

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	Dorsal hippocampal NMDA receptor blockade impairs extinction of naloxone-precipitated conditioned place aversion in acute morphine-treated rats by suppressing ERK and CREB phosphorylation in the basolateral amygdala
	Wang, Wei-Sheng 1,2; Chen, Zhong-Guo 1; Liu, Wen-Tao 1; Chi, Zhi-Qiang2 ; He, Ling 1; Liu, Jing-Gen2
刊名	BRITISH JOURNAL OF PHARMACOLOGY
	2015-01
卷号	172 期号:2 页码:482-491
关键词	drug withdrawal extinction amygdala hippocampal
ISSN号	0007-1188
DOI	10.1111/bph.12671
文献子类	Article
英文摘要	Background and PurposeSubstantial evidence shows that negative reinforcement resulting from the aversive affective consequences of opiate withdrawal may play a crucial role in drug relapse. Understanding the mechanisms underlying the loss (extinction) of conditioned aversion of drug withdrawal could facilitate the treatment of drug addiction. Experimental ApproachNaloxone-induced conditioned place aversion (CPA) of Sprague-Dawley rats was used to measure conditioned aversion. An NMDA receptor antagonist and MAPK kinase inhibitor were applied through intracranial injections. The phosphorylation of ERK and cAMP response element-binding protein (CREB) was detected using Western blot. Key ResultsThe extinction of CPA behaviour increased the phosphorylation of ERK and CREB in the dorsal hippocampus (DH) and basolateral amygdala (BLA), but not in the central amygdala (CeA). Intra-DH injection of AP5 or intra-BLA injection of AP-5 or U0126 before extinction training significantly attenuated ERK and CREB phosphorylation in the BLA and impaired the extinction of CPA behaviour. Although intra-DH injections of AP-5 attenuated extinction training-induced activation of the ERK-CREB pathway in the BLA, intra-BLA injection of AP5 had no effect on extinction training-induced activation of the ERK-CREB pathway in the DH. Conclusions and ImplicationsThese results suggest that activation of ERK and CREB in the BLA and DH is involved in the extinction of CPA behaviour and that the DH, via a direct or indirect pathway, modulates the activity of ERK and CREB in the BLA through activation of NMDA receptors after extinction training. Understanding the mechanisms underlying the extinction of conditioned aversion could facilitate the treatment of drug addiction. Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit
资助项目	Ministry of Science and Technology of China[2013CB835100] ; Ministry of Science and Technology of China[2009CB522005] ; Ministry of Science and Technology of China[2012ZX09301001-005] ; Ministry of Science and Technology of China[2012BAI01B00] ; National Natural Science Foundation of China[81130087] ; National Natural Science Foundation of China[91232716] ; Committee of Science and Technology of Shanghai[13JC140680]
WOS关键词	SIGNAL-REGULATED KINASE ; LONG-TERM POTENTIATION ; CONTEXTUAL FEAR ; GLUTAMATE RECEPTORS ; ARRIVE GUIDELINES ; PREFRONTAL CORTEX ; GENE-EXPRESSION ; CENTRAL NUCLEUS ; MEMORY ; ACQUISITION
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000346826500022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276779]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Jing-Gen
作者单位	1.China Pharmaceut Univ, Dept Pharmacol, Nanjing, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Key Lab Receptor Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Wei-Sheng,Chen, Zhong-Guo,Liu, Wen-Tao,et al. Dorsal hippocampal NMDA receptor blockade impairs extinction of naloxone-precipitated conditioned place aversion in acute morphine-treated rats by suppressing ERK and CREB phosphorylation in the basolateral amygdala[J]. BRITISH JOURNAL OF PHARMACOLOGY,2015,172(2):482-491.
APA	Wang, Wei-Sheng,Chen, Zhong-Guo,Liu, Wen-Tao,Chi, Zhi-Qiang,He, Ling,&Liu, Jing-Gen.(2015).Dorsal hippocampal NMDA receptor blockade impairs extinction of naloxone-precipitated conditioned place aversion in acute morphine-treated rats by suppressing ERK and CREB phosphorylation in the basolateral amygdala.BRITISH JOURNAL OF PHARMACOLOGY,172(2),482-491.
MLA	Wang, Wei-Sheng,et al."Dorsal hippocampal NMDA receptor blockade impairs extinction of naloxone-precipitated conditioned place aversion in acute morphine-treated rats by suppressing ERK and CREB phosphorylation in the basolateral amygdala".BRITISH JOURNAL OF PHARMACOLOGY 172.2(2015):482-491.