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Title: Opiate withdrawal induces dynamic-expressions of AMPA receptors and its regulatory molecule CaMKII alpha in hippocampal synapses
Author: Zhong, Weixia ; Dong, Zhifang ; Tian, Meng ; Cao, Jun ; Xu, Tianle(徐天乐) ; Xu, Lin ; Luo, Jianhong
Source: LIFE SCIENCES
Issued Date: 2006
Volume: 79, Issue:9, Pages:861-869
Keyword: AMPA receptor ; phosphorylation ; CaMKII alpha ; opiate withdrawal ; synaptosome ; LONG-TERM POTENTIATION ; PROTEIN-KINASE-II ; VENTRAL TEGMENTAL AREA ; RAT CEREBRAL-CORTEX ; SYNAPTIC PLASTICITY ; CHRONIC MORPHINE ; GLUCOCORTICOID-RECEPTOR ; STRESS ; COCAINE ; TRAFFICKING
Subject: Research & Experimental Medicine ; Pharmacology & Pharmacy
Corresponding Author: Luo, JH (reprint author), Zhejiang Univ, Sch Med, Dept Neurobiol, Hangzhou 310006, Peoples R China,lxu@vip.163.com
English Abstract: Adaptive changes in brain areas following drug withdrawal are believed to contribute to drug seeking and relapse. Cocaine withdrawal alters the expression of GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in nucleus accumbens or amygdala, but the influence of drug withdrawal on hippocampus is little known. Here, we have examined the expression of GluR1 and GluR2/3 in hippocampal membrane and synaptic fractions following repeated morphine exposure and subsequent withdrawal. Repeated morphine exposure for 12 d increased GluR1 and GluR2/3 in synaptosome but not in membrane fraction. Interestingly, CaMKII alpha, known to be able to regulate the function of AMPA receptors, was decreased in synaptosome but not in membrane fraction; pCaMKII alpha, the phosphorylated form of CaMKII alpha, was increased in both fractions. However, during opiate withdrawal, GluR1 was generally reduced while GluR2/3 was prominently increased in both fractions; pCaMKII alpha was strongly decreased immediately after withdrawal, but detectably increased in late phase of morphine withdrawal in both fractions. Importantly, the opiate withdrawal-induced increase in GluR2/3 was dependent on the activation of glucocorticoid receptors and NMDA receptors, as it was prevented by the glucocorticoid receptor antagonist RU38486, or intrahippocampal injection of the NMDA receptor antagonist AP-5 or the antagonist to NR2B-containing NMDA receptors, Ro25-6981. These findings indicate that opiate withdrawal induces dynamic expression of GluR1 and GluR2/3 subunits of AMPA receptors in hippocampal synapses, possibly revealing an adaptive process of the hippocampal functions following opiate withdrawal. (c) 2006 Elsevier Inc. All rights reserved.
Indexed Type: SCI
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1811
Appears in Collections:神经所(总)_期刊论文

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Zhong, Weixia; Dong, Zhifang; Tian, Meng; Cao, Jun; Xu, Tianle; Xu, Lin; Luo, Jianhong.Opiate withdrawal induces dynamic-expressions of AMPA receptors and its regulatory molecule CaMKII alpha in hippocampal synapses,LIFE SCIENCES,2006,79(9):861-869
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