The dose dependent effects of Pimavanserin on a modified rodent model of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a persistent psychiatric disorder where patients develop symptoms from directly experiencing or witnessing traumatic events. The animal models are often used as preclinical studies for PTSD. Our research group previously found that the developed animal model of PTSD, which was composed of chronic and acute stress, successfully induced PTSD-like anxiety behaviors in the three behavioral measurements: elevated-plus maze, open field, and acoustic startle response. Additionally, the inverse antagonist drug Pimavanserin significantly reduced these fear-related behaviors in the animal model. In the current research, we examined the effects of each stressor, specifically the effect of social isolation, in addition to the replication of the effects of Pimavanserin on the animal model of PTSD, including the dose dependence of Pimavanserin. As a result, higher dose injections significantly reduced rats’ anxiety-level in the behavioral measures, while the smaller and no Pimavanserin injections did not change animals’ behaviors. In relation to the effect of social isolation, there was no significant difference between animals in the single housed group and pair housed group. These results strongly supported the role of 5-HT2A in our PTSD-animal model. Furthermore, from the results, it is highly expected that the 5-HT2A receptors’ inverse antagonists have positive therapeutic effects on PTSD patients.