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Inhibition of PKM xi in Nucleus Accumbens Core Abolishes Long-Term Drug Reward Memory
Li, Yan-qin1; Xue, Yan-xue1; He, Ying-ying1; Li, Fang-qiong1; Xue, Li-fen1; Xu, Chun-mei1; Sacktor, Todd Charlton2,3; Shaham, Yavin4; Lu, Lin1
刊名JOURNAL OF NEUROSCIENCE
2011-04-06
DOI10.1523/JNEUROSCI.5884-10.2011
31期:14页:5436-5446
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
资助者National Basic Research Program of China ; Natural Science Foundation of China ; Natural Science Foundation of Beijing Municipality ; National Institute on Drug Abuse [National Institutes of Health (NIH), Department of Health and Human Services] ; National Institutes of Health ; National Basic Research Program of China ; Natural Science Foundation of China ; Natural Science Foundation of Beijing Municipality ; National Institute on Drug Abuse [National Institutes of Health (NIH), Department of Health and Human Services] ; National Institutes of Health
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]PROTEIN-KINASE-C ; DOPAMINE D-1-FAMILY RECEPTORS ; VENTRAL TEGMENTAL AREA ; AMPA RECEPTORS ; HEROIN SEEKING ; M-ZETA ; BASOLATERAL AMYGDALA ; SIGNALING PATHWAY ; COCAINE-SEEKING ; LTP MAINTENANCE
英文摘要

During abstinence, memories of drug-associated cues persist for many months, and exposure to these cues often provokes relapse to drug use. The mechanisms underlying the maintenance of these memories are unknown. A constitutively active atypical protein kinase C (PKC) isozyme, protein kinase M xi (PKM xi), is required for maintenance of spatial memory, conditioned taste aversion, and other memory forms. We used conditioned place preference (CPP) and conditioned place aversion (CPA) procedures to study the role of nucleus accumbens PKM xi in the maintenance of drug reward and aversion memories in rats. Morphine CPP training (10 mg/kg, 4 pairings) increased PKM xi levels in accumbens core but not shell. Injections of the PKM xi inhibitor xi inhibitory peptide (ZIP) into accumbens core but not shell after CPP training blocked morphine CPP expression for up to 14 d after injections. This effect was mimicked by the PKC inhibitor chelerythrine, which inhibits PKM xi, but not by the conventional and novel PKC inhibitor staurosporine, which does not effectively inhibit PKM xi. ZIP injections into accumbens core after training also blocked the expression of cocaine (10 mg/kg) and high-fat food CPP but had no effect on CPA induced by naloxone-precipitated morphine withdrawal. Accumbens core injections of Tat-GluR2(3Y), which inhibits GluR2-dependent AMPA receptor endocytosis, prevented the impairment in morphine CPP induced by local ZIP injections, indicating that the persistent effect of PKM xi is on GluR2-containing AMPA receptors. Results indicate that PKM xi activity in accumbens core is a critical cellular substrate for the maintenance of memories of relapse-provoking reward cues during prolonged abstinence periods.

语种英语
所属项目编号2009CB522004 ; 30725016 ; 09G0762 ; MH057068 ; MH53576
资助者National Basic Research Program of China ; Natural Science Foundation of China ; Natural Science Foundation of Beijing Municipality ; National Institute on Drug Abuse [National Institutes of Health (NIH), Department of Health and Human Services] ; National Institutes of Health ; National Basic Research Program of China ; Natural Science Foundation of China ; Natural Science Foundation of Beijing Municipality ; National Institute on Drug Abuse [National Institutes of Health (NIH), Department of Health and Human Services] ; National Institutes of Health
WOS记录号WOS:000289213500029
Citation statistics
Cited Times:70[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53736
Collection中国药物依赖性研究所
作者单位1.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
2.Suny Downstate Med Ctr, Dept Physiol & Pharmacol, New York, NY 11203 USA
3.Suny Downstate Med Ctr, Dept Neurol, New York, NY 11203 USA
4.Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA
Recommended Citation
GB/T 7714
Li, Yan-qin,Xue, Yan-xue,He, Ying-ying,et al. Inhibition of PKM xi in Nucleus Accumbens Core Abolishes Long-Term Drug Reward Memory[J]. JOURNAL OF NEUROSCIENCE,2011,31(14):5436-5446.
APA Li, Yan-qin.,Xue, Yan-xue.,He, Ying-ying.,Li, Fang-qiong.,Xue, Li-fen.,...&Lu, Lin.(2011).Inhibition of PKM xi in Nucleus Accumbens Core Abolishes Long-Term Drug Reward Memory.JOURNAL OF NEUROSCIENCE,31(14),5436-5446.
MLA Li, Yan-qin,et al."Inhibition of PKM xi in Nucleus Accumbens Core Abolishes Long-Term Drug Reward Memory".JOURNAL OF NEUROSCIENCE 31.14(2011):5436-5446.
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