Conditioned fear stress combined with single-prolonged stress: a new PTSD mouse model

There are still some defects in current single-prolonged stress (SPS) model and conditioned fear (CF) stress model of post-traumatic stress disorder (PTSD). The purpose of this study is to evaluate a novel mouse model of PTSD. Male KM mice suffered the double stresses-SPS and CF. After incubation time, the novel model exhibited the PTSD-like behaviors: sensitive fear and conditioned fear, low activities and defects in novel object recognition abilities. The apoptosis in the hippocampus was significantly increased, which was induced by the double stresses and further caused the synaptic structure damages in the hippocampus. The electron microscopy analysis further proved the synaptic losses and neuronal impairments in the hippocampus. Our results indicated this combined stresses mouse model was better than the SPS model and CF model. In addition, in order to further verify this model, paroxetine was administered after the double stresses. The results showed that paroxetine administration reduced PTSD-like behaviors, hippocampal apoptosis and structure damages. We conclude that this mouse model is novel and more predictably mimicked the clinical characteristics of PTSD, and this model can be further used for investigating the mechanisms of PTSD and screening effective therapeutics agents.