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eIF2 alpha Dephosphorylation in Basolateral Amygdala Mediates Reconsolidation of Drug Memory
Jian, Min1,2,3; Luo, Yi-Xiao1,2,3; Xue, Yan-Xue3; Han, Ying1,2,3; Shi, Hai-Shui4; Liu, Jian-Feng1,2,3; Yan, Wei1,2,3; Wu, Ping3; Meng, Shi-Qiu1,2,3; Deng, Jia-Hui1,2,3; Shen, Hao-Wei3; Shi, Jie3; Lu, Lin1,2,3,5,6
刊名JOURNAL OF NEUROSCIENCE
2014-07-23
DOI10.1523/JNEUROSCI.0934-14.2014
34期:30页:10010-10021
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]TERM SYNAPTIC PLASTICITY ; NUCLEUS-ACCUMBENS CORE ; FOOTSHOCK-INDUCED REINSTATEMENT ; COCAINE-SEEKING BEHAVIOR ; SIGNAL-REGULATED KINASE ; TRANSLATIONAL CONTROL ; MAMMALIAN TARGET ; PROTEIN-SYNTHESIS ; REWARD MEMORY ; CONSOLIDATION
英文摘要

Maladaptive memories elicited by exposure to environmental stimuli associated with drugs of abuse are often responsible for relapse among addicts. Interference with the reconsolidation of drug memory can inhibit drug seeking. Previous studies have indicated that the dephosphorylation of the eukaryotic initiation factor 2 alpha-subunit (eIF2 alpha) plays an important role in synaptic plasticity and long-term memory consolidation, but its role in the reconsolidation of drug memory remains unknown. The amygdala is required for the reconsolidation of a destabilized drug memory after retrieval of drug-paired stimuli. Here, we used conditioned place preference (CPP) and self-administration procedures to determine whether amygdala eIF2 alpha dephosphorylation is required for the reconsolidation of morphine and cocaine memories in rats. We found that the levels of eIF2 alpha phosphorylation (Ser51) and activating transcription factor 4 (ATF4) were decreased after reexposure to a previously morphine- or cocaine-paired context (i.e., a memory retrieval procedure) in the basolateral amygdala (BLA) but not in the central amygdala. Intra-BLA infusions of Sal003, a selective inhibitor of eIF2 alpha dephosphorylation, immediately after memory retrieval disrupted the reconsolidation of morphine- or cocaine-induced CPP, leading to a long-lasting suppression of drug-paired stimulus-induced craving. Advanced knockdown of ATF4 expression in the BLA by lentivirus-mediated short-hairpin RNA blocked the disruption of the reconsolidation of morphine-induced CPP induced by Sal003 treatment. Furthermore, inhibition of eIF2 alpha dephosphorylation in the BLA immediately after light/tone stimulus retrieval decreased subsequent cue-induced heroin-seeking behavior in the self-administration procedure. These results demonstrate that eIF2 alpha dephosphorylation in the BLA mediates the memory reconsolidation of drug-paired stimuli.

语种英语
WOS记录号WOS:000341001600018
项目编号31230033 ; 81221002 ; 81225009 ; 31300930 ; 2011CB707805
资助机构Natural Science Foundation of China ; National Basic Research Program of China
引用统计
被引频次:25[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/400002259/55023
专题北京大学精神卫生研究所
北京大学医学部管理机构_医学部
中国药物依赖性研究所
北京大学第三临床医学院_呼吸科
北京大学精神卫生研究所_精神科
作者单位1.Peking Univ, Inst Mental Hlth, Hosp 6, Beijing 100191, Peoples R China
2.Peking Univ, Key Lab Mental Hlth, Beijing 100191, Peoples R China
3.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
4.Hebei Med Univ, Dept Biochem & Mol Biol, Basic Med Coll, Shijiazhuang 050017, Peoples R China
5.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
6.Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Jian, Min,Luo, Yi-Xiao,Xue, Yan-Xue,et al. eIF2 alpha Dephosphorylation in Basolateral Amygdala Mediates Reconsolidation of Drug Memory[J]. JOURNAL OF NEUROSCIENCE,2014,34(30):10010-10021.
APA Jian, Min.,Luo, Yi-Xiao.,Xue, Yan-Xue.,Han, Ying.,Shi, Hai-Shui.,...&Lu, Lin.(2014).eIF2 alpha Dephosphorylation in Basolateral Amygdala Mediates Reconsolidation of Drug Memory.JOURNAL OF NEUROSCIENCE,34(30),10010-10021.
MLA Jian, Min,et al."eIF2 alpha Dephosphorylation in Basolateral Amygdala Mediates Reconsolidation of Drug Memory".JOURNAL OF NEUROSCIENCE 34.30(2014):10010-10021.
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