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An Unconditioned Stimulus Retrieval Extinction Procedure to Prevent the Return of Fear Memory
Liu, Jianfeng1,2,3; Zhao, Liyan1,2,3; Xue, Yanxue3; Shi, Jie3; Suo, Lin6; Luo, Yixiao3; Chai, Baisheng3,7,8; Yang, Chang1,2,7,8; Fang, Qin7,8; Zhang, Yan3; Bao, Yanping3; Pickens, Charles L.9; Lu, Lin1,2,3,4,5
关键词Extinction fear memory hippocampus reconsolidation retrieval unconditioned stimulus
刊名BIOLOGICAL PSYCHIATRY
2014-12-01
DOI10.1016/j.biopsych.2014.03.027
76期:11页:895-901
收录类别SCI ; SSCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences ; Psychiatry
研究领域[WOS]Neurosciences & Neurology ; Psychiatry
关键词[WOS]POSTTRAUMATIC-STRESS-DISORDER ; CONDITIONED FEAR ; CONTEXTUAL FEAR ; EXPOSURE THERAPY ; D-CYCLOSERINE ; RECONSOLIDATION ; AMYGDALA ; CONSOLIDATION ; RELAPSE ; HUMANS
英文摘要

Background: Conditioned fear memories can be updated by extinction during reconsolidation, and this effect is specific to the reactivated conditioned stimulus (CS). However, a traumatic event can be associated with several cues, and each cue can potentially trigger recollection of the event. We introduced a technique to target all diverse cues associated with an aversive event that causes fear.

Methods: In human experiments, 161 subjects underwent modified fear conditioning, in which they were exposed to an unconditioned stimulus (US) or unreinforced CS to reactivate the memory and then underwent extinction, spontaneous recovery, and reinstatement. In animal experiments, 343 rats underwent contextual fear conditioning under a similar protocol as that used in the human experiments. We also explored the molecular alterations after US reactivation in rats.

Results: Presentation of a lower intensity US before extinction disrupted the associations between the different CS and reactivated US in both humans and rats. This effect persisted for at least 6 months in humans and was selective to the reactivated US. This procedure was also effective for remote memories in both humans and rats. Compared with the CS, the US induced stronger endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptors 1 and 2 and stronger activation of protein kinase A, p70S6 kinase, and cyclic adenosine monophosphate response element binding protein in the dorsal hippocampus in rats.

Conclusions: These findings demonstrate that a modified US retrieval extinction strategy may have a potential impact on therapeutic approaches to prevent the return of fear.

语种英语
WOS记录号WOS:000344733200012
项目编号2011CB707805 ; 31230033 ; 31100809 ; 81221002 ; 81225009
资助机构National Basic Research Program of China ; Natural Science Foundation of China ; National Institutes of Health/National Institute on Drug Abuse
引用统计
被引频次:31[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/400002259/59557
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
作者单位1.Peking Univ, Inst Mental Hlth, Beijing 100191, Peoples R China
2.Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing 100191, Peoples R China
3.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
4.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100191, Peoples R China
5.China MeiTan Gen Hosp, Dept Pharm, Beijing, Peoples R China
6.Guiyang Med Univ, Sch Pharm, Guiyang, Peoples R China
7.Guiyang Med Univ, Affiliated Hosp, Guiyang, Peoples R China
8.Peking Univ, Int Data Grp, McGovern Inst Brain Res, Beijing 100191, Peoples R China
9.NIDA, Intramural Res Program, NIH, Baltimore, MD USA
推荐引用方式
GB/T 7714
Liu, Jianfeng,Zhao, Liyan,Xue, Yanxue,et al. An Unconditioned Stimulus Retrieval Extinction Procedure to Prevent the Return of Fear Memory[J]. BIOLOGICAL PSYCHIATRY,2014,76(11):895-901.
APA Liu, Jianfeng.,Zhao, Liyan.,Xue, Yanxue.,Shi, Jie.,Suo, Lin.,...&Lu, Lin.(2014).An Unconditioned Stimulus Retrieval Extinction Procedure to Prevent the Return of Fear Memory.BIOLOGICAL PSYCHIATRY,76(11),895-901.
MLA Liu, Jianfeng,et al."An Unconditioned Stimulus Retrieval Extinction Procedure to Prevent the Return of Fear Memory".BIOLOGICAL PSYCHIATRY 76.11(2014):895-901.
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