Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A(1) Receptors

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	Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A(1) Receptors
	Lu, Gang ; Zhou, Qi-Xin ; Kang, Shuo ; Li, Qing-Lin ; Zhao, Liang-Cai ; Chen, Jia-Dong ; Sun, Jian-Feng ; Cao, Jun ; Wang, Yu-Jun ; Chen, Jie ; Chen, Xiao-Yan ; Zhong, Da-Fang ; Chi, Zhi-Qiang ; Xu, Lin ; Liu, Jing-Gen
刊名	JOURNAL OF NEUROSCIENCE
	2010
卷号	30 期号:14 页码:5058-5070
关键词	PROTEIN-KINASE-C CENTRAL-NERVOUS-SYSTEM RAT HIPPOCAMPUS NUCLEOSIDE TRANSPORT NUCLEUS-ACCUMBENS SYNAPTIC PLASTICITY DOPAMINE-RECEPTORS OPIATE WITHDRAWAL BETA ISOFORMS GABA RELEASE
ISSN号	0270-6474
通讯作者	Liu, JG (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China,lxu@vip.163.com ; jgliu@mail.shcnc.ac.cn
英文摘要	Chronic exposure to opiates impairs hippocampal long-term potentiation (LTP) and spatial memory, but the underlying mechanisms remain to be elucidated. Given the well known effects of adenosine, an important neuromodulator, on hippocampal neuronal excitability and synaptic plasticity, we investigated the potential effect of changes in adenosine concentrations on chronic morphine treatment-induced impairment of hippocampal CA1 LTP and spatial memory. We found that chronic treatment in mice with either increasing doses (20-100 mg/kg) of morphine for 7 d or equal daily dose (20 mg/kg) of morphine for 12 d led to a significant increase of hippocampal extracellular adenosine concentrations. Importantly, we found that accumulated adenosine contributed to the inhibition of the hippocampal CA1 LTP and impairment of spatial memory retrieval measured in the Morris water maze. Adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine significantly reversed chronic morphine-induced impairment of hippocampal CA1 LTP and spatial memory. Likewise, adenosine deaminase, which converts adenosine into the inactive metabolite inosine, restored impaired hippocampal CA1 LTP. We further found that adenosine accumulation was attributable to the alteration of adenosine uptake but not adenosine metabolisms. Bidirectional nucleoside transporters (ENT2) appeared to play a key role in the reduction of adenosine uptake. Changes in PKC-alpha/beta activity were correlated with the attenuation of the ENT2 function in the short-term (2 h) but not in the long-term (7 d) period after the termination of morphine treatment. This study reveals a potential mechanism by which chronic exposure to morphine leads to impairment of both hippocampal LTP and spatial memory.
学科主题	Neurosciences & Neurology
收录类别	SCI
资助信息	Ministry of Science and Technology of China[G2003CB515400, 2009CB522000, 2009ZX09301-001, 2006CB500808]; National Natural Science Foundation of China[30425002]; National Science Fund of China[30873050, 30530250]; Chinese Academy of Sciences[KSCXI/YW/R/68]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1600]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Lu, Gang,Zhou, Qi-Xin,Kang, Shuo,et al. Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A(1) Receptors[J]. JOURNAL OF NEUROSCIENCE,2010,30(14):5058-5070.
APA	Lu, Gang.,Zhou, Qi-Xin.,Kang, Shuo.,Li, Qing-Lin.,Zhao, Liang-Cai.,...&Liu, Jing-Gen.(2010).Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A(1) Receptors.JOURNAL OF NEUROSCIENCE,30(14),5058-5070.
MLA	Lu, Gang,et al."Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A(1) Receptors".JOURNAL OF NEUROSCIENCE 30.14(2010):5058-5070.