Molecular targets for the interactive effect of etazolate during post-traumatic stress disorder: Role of oxidative stress, BDNF and histones.

Post-traumatic stress disorder (PTSD) develops in individuals after exposure to severe, life-threatening traumatic event. Etazolate is a selective phosphodiesterase IV inhibitor that is highly specific for cAMP, which has anxiolytic and antidepressant effects. We have previously shown that PTSD induced-memory impairment, anxiety and depression were prevented via the administration of etazolate. In the current study, the effect of etazolate on oxidative stress parameters, BDNF, and histone acetylation in the hippocampus were evaluated in a rat model of PTSD. The PTSD was induced by single prolonged stress (SPS) model. Etazolate was administered orally at a dose of 1 mg/kg/day for one month. At the end of the treatment period, the hippocampus was dissected and oxidative stress biomarkers (GSH, GSSG, GPx and TBARS), BDNF protein level, and histone acetylation were assessed. Results revealed that PTSD potentiated oxidative stress in the hippocampus and induced significant reductions in BDNF level and histones acetylation (P < 0.05). Etazolate treatment, on the other hand, led to prevention of changes in these oxidative stress biomarkers (GSH, GSSG, GPx and TBARS), BDNF levels, and histones acetylation. In conclusion, oxidative stress and modulation of BDNF and histones acetylation induced by PTSD can be prevented by treatment with etazolate.