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学科主题: 药物依赖
题名:
Inhibition of PKM xi in Nucleus Accumbens Core Abolishes Long-Term Drug Reward Memory
作者: 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
发表日期: 2011-04-06
DOI: 10.1523/JNEUROSCI.5884-10.2011
卷: 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
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
项目资助者: 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
WOS记录号: WOS:000289213500029
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53736
Appears in Collections:中国药物依赖性研究所_期刊论文

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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:
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.
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