title: Alterations in the hippocampal glycinergic system in an animal model of posttraumatic stress disorder.
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.
authors.affiliation: Department of Psychiatry and Neurosciences, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morinobu
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Yuto
authors.initials: Y
authors.lastname: Ueda
authors.forename: Shiro
authors.initials: S
authors.lastname: Takei
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fujita
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yamawaki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D004563:Electrochemistry / Q000379:methods; D005239:Fear / Q000523:psychology; D005786:Gene Expression Regulation / Q000502:physiology*; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000473:pathology*; D013997:Time Factors
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493266:Slc6a9 protein, rat; D005998:Glycine