Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Depress Anxiety. 2009;26(12):1110-7. doi: 10.1002/da.20629.
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.
尽管选择性 5-羟色胺再摄取抑制剂（SSRIs）被报道可有效减轻创伤后应激障碍（PTSD）症状，但仍有一部分 PTSD 患者持续存在症状，并保持对创伤性刺激的条件性恐惧反应。在这种情况下，建立适当的 PTSD 动物模型对于更好地理解该疾病的机制以及促进开发更有效的 SSRIs 替代治疗方法是必要的。尽管迄今为止尚未建立一个被广泛接受的 PTSD 动物模型，但单次延长应激（SPS）动物模型已部分验证为 PTSD 的模型。SPS 大鼠模拟了 PTSD 的病理生理异常和行为特征，例如焦虑样行为和糖皮质激素负反馈增强，并且对帕罗西汀增强的恐惧记忆表现出预期的治疗反应。此外，SPS 大鼠在情境性恐惧条件反射中表现出增强的冻结，以及恐惧记忆的消退受损，而 D-环丝氨酸可减轻这种损伤。SPS 大鼠中发现的恐惧记忆增强巩固和消退受损表明，该模型具有额外的价值，因为最近对 PTSD 的研究表明，记忆异常是其一个核心特征。在本研究中，我们总结了 SPS 中与 PTSD 样症状相关的行为和病理生理学变化，重点关注记忆异常，并评估 SPS 作为 PTSD 动物模型的有效性。
