Fatty acid amide hydrolase inhibitor URB597 suppressed conditioned and sensitized fear responses in a rat model of post-traumatic stress disorder

Abstract

BackgroundPost-traumatic stress disorder (PTSD) is a debilitating disorder that results from exposure to various traumatic events. Endocannabinoids levels change during PTSD. Inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for anandamide degradation, has shown potential in treating PTSD. MethodsWe used male Wistar rats and single prolonged stress plus shock as the experimental model of PTSD-like phenotype. Freezing times during conditioned fear response (CFR) and sensitized fear response (SFR) were recorded. The effect of URB597 (0.1, 0.3, and 0.6 mg/kg), a FAAH inhibitor, and fluoxetine (10 mg/kg) as control drug on CFR and SFR were evaluated for two weeks. After the test, the anxiety-like and depression-like behaviors of the animals were assessed by elevated plus-maze and forced swim test, respectively. The serum concentration of corticosterone was also measured at the end of the experiments. ResultsThe results showed that fluoxetine and URB597 suppressed freezing time in both CFR and SFR procedures. The drugs showed apparent anxiolytic-like and antidepressant-like effects. URB597 at the dose of 0.6 mg/kg decreased corticosterone level. ConclusionsThe results of the present study showed that URB597 induced a protective effect against experimental PTSD-like phenotype. Regarding its anxiolytic-like and antidepressant-like effects, the drug may be suggested as a potential treatment for PTSD.