ABSTRACT
Abstract Crocus sativus L., Iridaceae, has been used worldwide in traditional medicinefor treatment ofsome neurological disorderssuch as depression. Post-traumatic stress disorder is a mental disorder developed in peoplewho experience stressful events. Since stress has been proposed tocause thehypothalamic-pituitary-adrenal axis malfunction in post-traumatic stress disorder patients, this study aimed at investigating the effect of saffron aqueous extract on hypothalamic-pituitary-adrenal axis activity in rats of post-traumatic stress disorder model. Here, Post-traumatic stress disorder animals received an acute electro foot shock; however, 5 min before the stress session, these animals received an intra-cerebral-ventricular (10 µg/rat) infusion of either saffron aqueous extract or saline. Twenty one days later, they were re-exposedto the stress box withoutinducing stress, andthen were examined for their freezing behavior. The impact of stress and saffron aqueous extract on serum corticosterone, corticotrophin releasing hormone gene expression in hypothalamus and glucocorticoid receptor gene expression in pituitary gland werethen evaluated on day 28. Intra-cerebral-ventricular injection of saffron aqueous extract resulted in an increase in serum corticosterone level and reduced symptoms of freezing behavior, and corticotrophin releasing hormone and glucocorticoid receptor gene expression in post-traumatic stress disorder groups.Saffron administration could improve the symptoms of stress-induced post-traumatic stress disorder, possiblythrough the adjustment ofhypothalamic-pituitary-adrenal axis function.