Yamamoto Shigeto
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.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2009 Jun;29(3):135-9.
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. In this study, using rats subjected to single prolonged stress (SPS), an animal model of PTSD, 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. 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, suggesting 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. Our research indicates that DCS may be a promising tool for the treatment of PTSD.
尽管创伤性记忆消退受损是创伤后应激障碍（PTSD）的标志性症状之一，但消退受损的潜在机制尚不清楚，且尚未开发出有效的药物干预措施。在本研究中，我们使用遭受单次长时间应激（SPS）的大鼠（一种PTSD动物模型），研究了以下内容：（a）SPS损害恐惧消退的能力；（b）D-环丝氨酸（DCS）是否能减轻SPS大鼠的恐惧消退受损；（c）在消退训练期间，SPS和/或DCS对大鼠海马体中N-甲基-D-天冬氨酸（NMDA）受体亚基mRNA水平的影响。SPS大鼠在情境恐惧测试中表现出恐惧消退受损，而重复给予DCS可使其得到缓解。SPS在消退训练前和训练期间诱导NMDA受体亚基mRNA水平显著上调，而重复给予DCS可消除NMDARs增强的mRNA水平，这表明DCS可能有助于逆转海马体可塑性，从而逆转NMDA的代偿性改变，无论其在增强恐惧消退中的机制如何。我们的研究表明，DCS可能是治疗PTSD的一种有前景的工具。
