Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses

	Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses
	Xu, NJ; Bao, L; Fan, HP; Bao, GB; Pu, L; Lu, YJ; Wu, CF; Zhang, X; Pei, G
刊名	JOURNAL OF NEUROSCIENCE
	2003
卷号	23 期号:11 页码:4775-4784
关键词	morphine rat hippocampus glutamate transporter GLT1 opiate withdrawal
通讯作者	Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,
英文摘要	Opiate abuse causes adaptive changes in several processes of synaptic transmission in which the glutamatergic system appears a critical element involved in opiate tolerance and dependence, but the underlying mechanisms remain unclear. In the present study, we found that glutamate uptake in hippocampal synaptosomes was significantly increased ( by 70% in chronic morphine-treated rats) during the morphine withdrawal period, likely attributable to an increase in the number of functional glutamate transporters. Immunoblot analysis showed that expression of GLT1 ( glutamate transporter subtype 1) was identified to be upregulated in synaptosomes but not in total tissues, suggesting a redistribution of glutamate transporter expression. Moreover, the increase in glutamate uptake was reproduced in cultured neurons during morphine withdrawal, and the increase of uptake in neurons could be blocked by dihydrokainate, a specific inhibitor of GLT1. Cell surface biotinylation and immunoblot analysis showed that morphine withdrawal produced an increase in GLT1 expression rather than EAAC1 ( excitatory amino acids carrier 1), a neuronal subtype, at the cultured neuronal cell surface, whereas no significant change was observed in that of cultured astrocytes. Electron microscopy also revealed that GLT1 expression was markedly increased in the nerve terminals of hippocampus and associated with the plasma membrane in vivo. These results suggest that GLT1 in hippocampal neurons can be induced to translocate to the nerve terminals and express on the cell surface during morphine withdrawal. The translocation of GLT1 at synapses during morphine withdrawal provides a neuronal mechanism for modulation of excitatory neurotransmission during opiate abuse.
学科主题	Neurosciences & Neurology
类目[WOS]	Neurosciences
关键词[WOS]	HIGH-AFFINITY GLUTAMATE ; LONG-TERM POTENTIATION ; PROTEIN-KINASE-C ; IN-VIVO MICRODIALYSIS ; RAT CORTICAL-NEURONS ; DORSAL-ROOT GANGLIA ; NUCLEUS-ACCUMBENS ; PRECIPITATED WITHDRAWAL ; ANTISENSE KNOCKDOWN ; PERIPHERAL AXOTOMY
收录类别	SCI
语种	英语
WOS记录号	WOS:000183443700040
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2363]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Xu, NJ,Bao, L,Fan, HP,et al. Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses[J]. JOURNAL OF NEUROSCIENCE,2003,23(11):4775-4784.
APA	Xu, NJ.,Bao, L.,Fan, HP.,Bao, GB.,Pu, L.,...&Pei, G.(2003).Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses.JOURNAL OF NEUROSCIENCE,23(11),4775-4784.
MLA	Xu, NJ,et al."Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses".JOURNAL OF NEUROSCIENCE 23.11(2003):4775-4784.