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ID 30879
file
creator
Yamamoto, Shigeto
Morinobu, Shigeru
Iwamoto, Yasuyuki
Ueda, Yuto
Takei, Shiro
Fujita, Yosuke
subject
Single prolonged stress
Fear extinction
Glycine
Glycine transporter 1
Hippocampus
Posttraumatic stress disorder
NDC
Medical sciences
abstract
Previous studies have demonstrated that rats subjected to single prolonged stress (SPS) exhibit posttraumatic stress disorder (PTSD)-like symptoms such as enhanced contextual fear in response to trauma related and trauma-unrelated events Furthermore we previously reported that upregulation of hippocampal glycine transporter 1 (GlyT-1) mRNA after context exposure could be the initial mechanism underlying impaired fear extinction in SPS rats To clarify the involvement of the hippocampal glycinergic system in impaired fear extinction in SPS rats we measured the time course of changes in the duration of freezing, and the hippocampal levels of Gly-T1 mRNA using contextual fear conditioning (FC) and extinction training We also used in vivo microdialysis to measure the concentration of extracellular glycine in the hippocampus during the time interval between FC and the first context exposure SPS rats exhibited increased and sustained contextual fear responses The enhanced contextual fear response in SPS rats was associated with a sustained increase in hippocampal levels of Gly-T1 mRNA after FC relative to sham rats and by a decrease in the extracellular glycine concentration GlyT-1 mRNA levels in rats that underwent repeated extinction training were significantly lower than in rats that did not undergo extinction training These findings indicate that reduced activity of the hippocampal glycinergic system could be closely involved in impaired fear extinction in SPS rats suggesting that activation of the glycinergic system by D-cycloserine or GlyT-1 inhibitors may ameliorate the impairment of fear extinction.
journal title
Journal of Psychiatric Research
volume
Volume 44
issue
Issue 15
start page
1069
end page
1074
date of issued
2010-11
publisher
Pergamon Elsevier Science Ltd
issn
0022-3956
ncid
publisher doi
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2010 Elsevier Ltd.
relation url
department
Graduate School of Biomedical Science