Present status and prospects about an animal model of post-traumatic stress disorder in rats using a shuttle box]

Wistar rats exposed to inescapable foot shocks (IS) for 2 wk exhibited PTSD-like bi-directional changes similar to avoidance/numbing and hyperarousal symptoms when placed in a shuttle box. Paroxetine administration after IS reduced the hyperarousal-like behavior, and its therapeutic effect on avoidance/numbing-like behavior was also significant. Further, F344 rats, which were more vulnerable to various kinds of stressors, showed more significant 'bi-directional changes' than Wistar rats. Thus, the paradigm we have developed could serve as a useful PTSD model because of its face, predictive, and construct validity. Moreover, the intensity of IS dose-dependently induced PTSD-like behaviors and hypo-activity in a shuttle box, similar to the 'avoidance/numbing' that reappeared in a square open field. These findings further support the construct validity of this paradigm. Both electro-convulsive shock treatment before and after IS ameliorated the PTSD-like behaviors in this model, so electro-convulsive therapy may be an effective method for prevention and medical treatment of PTSD in the future. On the other hand, pretreatment with fluvoxamine before IS did not have a significant effect, and its improving effect after IS was only observed for 'hyperarousal' behavior. Lastly, we recently developed a useful criterion, which is represented as a 'bi-directional index', for separating real PTSD rats from those exposed to IS.