The effects of chronic valproate and diazepam in a mouse model of posttraumatic stress disorder

To better understand neurochemical and psychopharmacological aspects of post-traumatic stress disorder (PTSD), it is necessary establish an animal model of PTSD in which behavioral changes persist for a long time after the initial traumatization. The present study aimed to characterize long-term behavioral alterations in male ICR mice as an animal model of PTSD consisting of a 2-day foot shock (0.8 mA, 10 s) followed by 3 weekly situational reminders (SR), and to evaluate the effects of repeated administration of valproate and diazepam on behavioral deficits of this animal model. The results showed that the aversive procedure induced several long-term behavioral deficiencies: increased freezing behavior and anxiety level, reduced time spent in an aversive like context. Repeated treatment with valproate (100-400 mg/kg, i.p.) induced a dose-dependent reduction of these behavioral changes. In contrast, diazepam at a low dose (0.25 mg/kg) but not at a high dose (4 mg/kg) reduced the behavioral deficiencies. These results demonstrate that exposure to intense foot shock associated with repeated situational reminders elicits long-term disturbances that last about 4 weeks after the foot shock exposure. These behavioral deficits can be ameliorated by repeated administration of valproate or diazepam at some special dose ranges.