[A novel therapeutic approach for the treatment of post-traumatic stress disorder (PTSD): enhancing the impaired extinction of fear memory].
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.
Yamamoto
Shigeto
S
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. shigeto1888@yahoo.co.jp
D000818:Animals; D005108:Extinction, Psychological; D005239:Fear / Q000523:psychology*; D008568:Memory; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000523:psychology*
D016194:Receptors, N-Methyl-D-Aspartate