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Central Amygdala Extracellular Signal-Regulated Kinase Signaling Pathway Is Critical to Incubation of Opiate Craving
Li, Yan-Qin1; Li, Fang-Qiong1; Wang, Xiao-Yi1; Wu, Ping1; Zhao, Mei1; Xu, Chun-Mei1; Shaham, Yavin2; Lu, Lin1
关键词Amygdala Morphine Conditioned Place Preference Incubation Erk Creb Relapse
刊名JOURNAL OF NEUROSCIENCE
2008-12-03
DOI10.1523/JNEUROSCI.3027-08.2008
28期:49页:13248-13257
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]CONDITIONED PLACE PREFERENCE ; ACTIVATED PROTEIN-KINASE ; ELEMENT-BINDING PROTEIN ; INDUCED COCAINE SEEKING ; VENTRAL TEGMENTAL AREA ; TIME-DEPENDENT CHANGES ; STRESS-INDUCED RELAPSE ; NUCLEUS-ACCUMBENS ; REINFORCING PROPERTIES ; INDUCED REINSTATEMENT
英文摘要

Cue-induced drug-seeking in rodents progressively increases after withdrawal from operant self-administration of cocaine, heroin, methamphetamine, and alcohol, a phenomenon termed "incubation of drug craving." Here, we used the opiate drug morphine and explored whether incubation of drug craving also occurs in a pavlovian conditioned place preference (CPP) procedure in which rats learn to associate drug effects with a distinct environmental context. We also explored the role of amygdala extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in this incubation. We found that the expression of morphine CPP progressively increases over the first 14 d after the last drug exposure in rats receiving four pairings of low-dose (1 or 3 mg/kg) but not high-dose (10 mg/kg) morphine with a distinct environment. The progressive increase in low-dose (3 mg/kg) morphine CPP was associated with increased ERK phosphorylation (a measure of ERK activity) and CREB( a downstream target of ERK) phosphorylation in central but not basolateral amygdala. Furthermore, inhibition of central but not basolateral amygdala ERK and CREB phosphorylation by U0126 [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene] decreased the enhanced ( incubated) drug CPP after 14 d of withdrawal from morphine. Finally, stimulation of central amygdala ERK and CREB phosphorylation by NMDA enhanced drug CPP after 1 d of withdrawal from morphine, an effect reversed by U0126. These findings indicate that the rat′s response to environmental cues previously paired with morphine progressively increases or incubates over the first 14 d of withdrawal from low but not high morphine doses. Additionally, this "incubation of morphine craving" is mediated by acute activation of central amygdala ERK pathway.

语种英语
WOS记录号WOS:000261378100024
项目编号2006AA02Z4D1 ; 2007CB512302 ; 2009CB522004 ; 30670713 ; 30725016
资助机构National High Technology Research and Development Program of China 863 Program ; National Basic Research Program of China ; Natural Science Foundation of China ; National Institute on Drug Abuse, Intramural Research Program
引用统计
被引频次:95[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52423
专题中国药物依赖性研究所
北京大学医学部管理机构_医学部
北京大学第三临床医学院_老年内科
作者单位1.Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China
2.NIDA, NIH, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA
推荐引用方式
GB/T 7714
Li, Yan-Qin,Li, Fang-Qiong,Wang, Xiao-Yi,et al. Central Amygdala Extracellular Signal-Regulated Kinase Signaling Pathway Is Critical to Incubation of Opiate Craving[J]. JOURNAL OF NEUROSCIENCE,2008,28(49):13248-13257.
APA Li, Yan-Qin.,Li, Fang-Qiong.,Wang, Xiao-Yi.,Wu, Ping.,Zhao, Mei.,...&Lu, Lin.(2008).Central Amygdala Extracellular Signal-Regulated Kinase Signaling Pathway Is Critical to Incubation of Opiate Craving.JOURNAL OF NEUROSCIENCE,28(49),13248-13257.
MLA Li, Yan-Qin,et al."Central Amygdala Extracellular Signal-Regulated Kinase Signaling Pathway Is Critical to Incubation of Opiate Craving".JOURNAL OF NEUROSCIENCE 28.49(2008):13248-13257.
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