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ID 25924
本文ファイル
著者
Yamamoto, Shigeto
Morinobu, Shigeru
Kurata, Akiko
Kozuru, Toshiro
キーワード
posttraumatic stress disorder (PTSD)
single prolonged stress (SPS)
extinction
contextual fear conditioning
NMDA receptor subunits (NMDARs)
D-cycloserine (DCS)
NDC
医学
心理学
抄録(英)
Although the impaired extinction of traumatic memory is one of the hallmark symptoms of PTSD, the underlying mechanisms of impaired extinction are unclear and effective pharmacological interventions have not yet been developed. Single prolonged stress (SPS) has been proposed as an animal model of PTSD, since rats subjected to SPS (SPS rats) show enhanced negative feedback of the HPA axis and increased contextual fear, which are characteristics similar to those observed in patients with PTSD. In this study, using SPS rats, we examined (a) the ability of SPS to impair fear extinction, (b) whether D-cycloserine (DCS) can alleviate impaired fear extinction in SPS rats, and (c) the effect of SPS and/or DCS on the levels of N-methyl-D-aspartate (NMDA) receptor subunit mRNAs in the rat hippocampus during extinction training. SPS rats exhibited impaired fear extinction in the contextual fear test, which was alleviated by the repeated administration of DCS. The effect of enhanced extinction, induced by the administration of DCS to SPS rats, was maintained for one week following extinction training. SPS induced significant upregulation of the levels of NMDA receptor subunit mRNAs before and during the period of extinction training, while repeated administration of DCS eliminated the enhanced mRNA levels of NMDARs. Behavioral analyses indicated that SPS is an appropriate animal model of PTSD and that DCS may be effective in the treatment of PTSD. These findings suggest that DCS, irrespective of its mechanistic involvement in the enhancement of fear extinction, may help to reverse hippocampal plasticity, and thus reverse the NMDA compensatory alterations.
掲載誌名
Neuropsychopharmacology
33巻
9号
開始ページ
2108
終了ページ
2116
出版年月日
2008
出版者
Nature Publishing Group
ISSN
0893-133X
NCID
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
Copyright (c) 2009 American College of Neuropsychopharmacology
関連情報URL
部局名
医歯薬学総合研究科