The Effects of Pimavanserin on Corticosterone Levels in a Rodent Model of Posttraumatic Stress Disorder

PTSD can affect individuals that have experienced or witnessed a traumatic event, resulting in numerous physical and psychiatric symptoms. Selective serotonin reuptake inhibitors (SSRIs) and behavior therapy are often applied to treat PTSD symptoms. Although they are rarely administered, atypical antipsychotic medication has beneficial outcomes in those suffering from severe PTSD symptoms. This study aims to investigate the effects of the antipsychotic drug, pimavanserin, on corticosterone in a rodent model of post-traumatic stress disorder. This study also aims to provide further validity to an existing rodent model of PTSD and the procedures commonly utilized to induce stress. The current model of PTSD is a result of social isolation and a repeated stress exposure procedure, which subjected the rodents to predator odor while restrained. Forty-eight female Lewis rats were included in this blinded study. Rodents were randomized to one of four equally sized groups: control group (sham-stress), pimavanserin high dose stressed group, pimavanserin low dose stressed group, or no treatment stressed group. The effects of isolation and two stress inducing events were measured by comparing corticosterone levels between the control group and stressed groups, independent of treatment. Additionally, the influence of pimavanserin on corticosterone levels and potential dose-dependent effects were measured. It was hypothesized that corticosterone levels would increase after rodents were subjected to single housing. Additionally, it was predicted that a decrease in stress hormone levels in the blood samples collected following the stress exposure for all groups, except for the non-stressed control group, would be observed. It was also hypothesized that higher levels of corticosterone would be measured among subjects treated with the antipsychotic drug, pimavanserin. Finally, results revealing dose dependent effects were predicted. It was hypothesized that a higher level of corticosterone would be observed in those treated with a higher dose of pimavanserin. Significant differences were also observed within subjects in the corticosterone concentrations collected on Day 8, Day 21, and Day 47. Specifically, stress hormone levels collected on Day 21 differed significantly from levels obtained on Day 8 and Day 47. These findings suggest a temporary effect of social isolation on stress response. Significant differences were observed between groups in corticosterone concentrations in the blood samples collected on Day 55, 24 days after stress exposure. These findings indicate a dose-dependent effect, as subjects that received the higher dose of pimavanserin produced the lowest corticosterone levels. Outcomes of this study will expand existing literature regarding the use of antipsychotics to treat PTSD symptoms and measures commonly utilized to induce stress in rodents.