Aqueous extract of saffron administration along with amygdala deep brain stimulation promoted alleviation of symptoms in post-traumatic stress disorder (PTSD) in rats

Objective: Post-traumatic stress disorder (PTSD) as one of the most devastating kinds of anxiety disorders, is the consequence of a traumatic event. Crocus sativus L., commonly known as saffron have been traditionally used for treatment of stress and anxiety. In this study, we evaluated the effects of peripheral administration of saffron, along with deep brain stimulation (DBS) in a post-traumatic stress disorder (PTSD) model caused by contextual fear conditioning (electrical foot shock chamber) in male Wistar rats. Materials and Methods: rats (220-250 g) were divided into 7 groups (n=8) and underwent stereotactic surgery for implantation of the electrodes in the right-baso lateral of the amygdala (BLA). After 7 days, some animals received the foot shock, followed by another 7-day treatment (DBS treatment or combination treatment by saffron 5 mg/kg (i.p)) then freezing behavior as a predicted response in the absence of the foot shock (re-exposure time) and general anxiety were measured using elevated plus maze test. Serum corticosterone level and amygdala c-Fos protein expression were assessed using ELISA and Western blot analysis, respectively. Results: DBS treatment and the combination therapy of saffron (5 mg/kg (I.P)) with DBS significantly (p<0.001) increased serum corticosterone levels. Also both treatments could significantly (p<0.001) reduce c-Fos protein expression and freezing behaviors time. However, DBS treatment had no effect on the general anxiety in rats with PTSD. On the other hand, combination therapy significantly (p<0.001) reduced anxiety behavior in rats with PTSD. Conclusion: These results might show the potential of this combination therapy for treatment of treatment-resistant PTSD patients.

Keywords:

Deep brain stimulation , Saffron , Post-traumatic stress disorder , Contextual fear conditioning , Corticosterone , C-Fos protein