An animal model of posttraumatic stress disorder in rats using a shuttle box]

We administered inescapable footshocks (IS) to male Wistar rats in a shuttle box, and after 2 weeks, an avoidance/escape task was performed in the same box. The rats exposed to IS 2 weeks beforehand exhibited PTSD-like bi-directional changes similar to symptoms of "avoidance/ numbing" and "hyperarousal". That is, in the relatively calm period just before the avoidance/escape task, spontaneous locomotor activities decreased. On the other hand, in the stressful situation after starting the task, not only responses to external stimuli but also locomotor activities increased. Thus, the paradigm we have used until now could serve as a useful PTSD model because of its "face validity". To demonstrate the greater validity, we administered paroxetine (PRX), which is effective for PTSD, to rats to examine its chronic effect on our model. We also substituted F344 rats, which are vulnerable to various stressors, for the Wistar rats to investigate the difference between the strains. Two weeks of PRX treatment significantly reduced hyperarousal-like behavior, and its ameliorating effect on avoidance/numbing-like behavior was also significant. F344 showed more significant 'bi-directional changes' than Wistar rats. These findings demonstrate that our paradigm is sufficiently valid for an animal model of PTSD, especially in "predictive validity" and "construct validity."