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

	Chronic Morphine Treatment Impaired Hippocampal Long-Term Potentiation and Spatial Memory via Accumulation of Extracellular Adenosine Acting on Adenosine A(1) Receptors
	Lu G 1; Zhou QX 2; Chen JD 4; Sun JF 1; Cao J 2; Wang YJ 1; Chen J 1; Chen XY1 ; Kang S 1; Zhong DF 1; Chi ZQ 1; Xu L2; Liu JG1; Li QL 3; Zhao LC 3; lxu@vip.163.com ; jgliu@mail.shcnc.ac.cn
	2010-08-16
发表期刊	JOURNAL OF NEUROSCIENCE
卷号	30 期号:14 页码:5058-5070
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.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/10848
专题	科研部门_学习记忆的分子神经机制（徐林）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	lxu@vip.163.com; jgliu@mail.shcnc.ac.cn
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models & Human Dis Mech, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China 3.Anhui Univ Tradit Chinese Med, Hefei 230032, Peoples R China 4.Chinese Acad Sci, State Key Lab Neurosci, Inst Neurosci, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Lu G,Zhou QX,Chen JD,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 G.,Zhou QX.,Chen JD.,Sun JF.,Cao J.,...&jgliu@mail.shcnc.ac.cn.(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 G,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.

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