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学科主题: 精神卫生
题名:
An Unconditioned Stimulus Retrieval Extinction Procedure to Prevent the Return of Fear Memory
作者: 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
发表日期: 2014-12-01
DOI: 10.1016/j.biopsych.2014.03.027
卷: 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
所属项目编号: 2011CB707805 ; 31230033 ; 31100809 ; 81221002 ; 81225009
项目资助者: National Basic Research Program of China ; Natural Science Foundation of China ; National Institutes of Health/National Institute on Drug Abuse
WOS记录号: WOS:000344733200012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59557
Appears in Collections:北京大学精神卫生研究所_期刊论文

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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

Recommended Citation:
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.
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