Abstract
Application of single prolonged stress (SPS) in rats induces changes in neuroendocrine function and arousal that are characteristic of post-traumatic stress disorder (PTSD). However, the SPS model's applicability to mice has not been established. In this study, we tried to clarify the applicability of a SPS paradigm as PTSD model in mice, which are useful to provide, genetic engineering techniques, such as genetic recombination or gene analysis. The SPS paradigm is conducted in three stages: animals are restrained for 2 h and immediately afterwards undergo a 20 min forced swim. Following recuperation for 15 min, the mice are exposed to ether until the loss of consciousness. The mice are then left in their home cage until a behavioral analysis is performed. To confirm the pathophysiology of PTSD, we first conducted hypothalamo-pituitary-adrenal (HPA) negative feedback testing at 1, 4, 8 and 12 weeks after the application of the paradigm by using dexamethasone (DEX) suppression test. Secondly, to investigate PTSD-like behavioral characteristics such as those affecting cognition, emotion, and motor activity, the mice were subjected to a light/dark box test (to assess anxiety), a Y-maze test (working memory), a cliff avoidance test (visual cognition), and an open field test (locomotor activity) were measured at 1, 4, 8 and 12 weeks after the application of the SPS paradigm in mice. In the light/dark box test, the SPS-applied mice spent significantly less time in the light box at 8 or 12 weeks after the application of the paradigm. In the cliff avoidance test, the SPS-applied mice spent significantly less time in the open area at 1 week after the application of the paradigm, although the time that both groups spent time in the open area had decreased gradually and time-dependently at 4 weeks after application. However, in both the Y-maze test and the open field test, SPS-applied mice tended toward slight decreases in a time-dependent manner until 12 weeks after the application. Therefore, SPS-applied mice may be useful for assessing characteristics relevant to PTSD that coincide with changes in the HPA axis, such as brain glucocorticoid systems.
