Although selective serotonin reuptake inhibitors (SSRIs) are reported to be effective in decreasing posttraumatic stress disorder (PTSD) symptoms, a subgroup of PTSD patients remain chronically symptomatic and maintain conditioned fear responses to traumatic stimuli. In this context, the establishment of an appropriate animal model of PTSD is necessary to promote better understanding of the mechanisms of the disorder and to facilitate the development of more effective therapeutic alternatives to SSRIs. Although no single widely accepted animal model of PTSD has been established to date, the single prolonged stress (SPS) animal model has been partially validated as a model for PTSD. SPS rats mimic the pathophysiological abnormalities and behavioral characteristics of PTSD, such as enhanced anxiety-like behavior and glucocorticoid negative feedback, and they exhibit the expected therapeutic response to paroxetine on enhanced fear memory. In addition, SPS rats exhibit enhanced freezing in response to contextual fear conditioning, and impaired extinction of fear memory, which is alleviated by D-cycloserine. The enhanced consolidation and impaired extinction of fear memory found in SPS rats suggests that this model has additional value because recent studies of PTSD indicate that memory abnormalities are a central feature. In this study, we summarize the behavioral and pathophysiological PTSD-like symptoms in SPS, focusing on memory abnormalities, and evaluate the validity of SPS as an animal model of PTSD.

Although the impaired extinction of traumatic memory is one of the hallmark symptoms of posttraumatic stress disorder (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.

2009). Single immobilization stress differentially alters the expression profile of transcripts of the brainderived neurotrophic factor ( BDNF) gene and histone acetylation at its promoters in the rat hippocampus. AbstractDecreased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus are implicated in the pathophysiology of major depression, although the mechanism has yet to be characterized. Epigenetic studies revealed that DNA methylation and histone modifications at the promoter of exons of the BDNF gene are the pivotal factors in the regulation of BDNF transcription. Histone acetylation regulates gene transcription through chromatin remodelling. We examined the influence of a single immobilization stress (SIS) at 2 h and 24 h afterwards on the levels of total BDNF mRNA with each exon mRNA by quantitative real-time PCR, acetylated histone at the promoters of the BDNF gene by chromatin immunoprecipitation followed by real-time PCR, and BDNF protein by ELISA in the rat hippocampus. SIS significantly decreased the levels of total BDNF mRNA with significantly reduced levels of exons I and IV mRNA followed by a significant reduction in BDNF protein 4 h after SIS. Significant decreases in the levels of acetylated histone H3, but not H4, were found at the promoters of exons I, IV, and VI. In contrast, no marked changes in the levels of either acetylated histone or BDNF mRNA and protein were found 24 h after SIS. This study demonstrated the involvement of histone acetylation in the regulation of BDNF transcription by SIS, and the plastic change in histone acetylation after SIS. These findings suggest that stress affects BDNF gene transcription via epigenetic regulation, and glucocorticoid may be involved in this regulation.

SUMMARYTen dairy cows were allocated into three groups according to milk productivity (four high, four intermediate and two dry cows, respectively). Heat production and heart rate, but not rectal temperature, were significantly different (P < 0·05) between groups. Heat production increased during feeding in the morning and in the afternoon and reached a peak 3 h later. Minimum heat production was observed in the early morning before feeding. The diurnal pattern for heart rate reflected that of heat production. These results suggest that cooling dairy cows during hot summer days is most effective at feeding time and 3 h afterwards.

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