Amelioration by Withania somnifera of neurobehavioural and immunological markers in time dependent sensitization induced post traumatic stress disorder in rats.

Abstract

Posttraumatic stress disorder (PTSD) is a complex neuropsychiatric pathophysiology with an unmet need for safe, effective, and sustainable therapeutic modalities. Thus, the present study evaluated the effects of Withaniasomnifera (WS, Ashwagandha) on an experimental model of PTSD in rats. Wistar rats (200-250 g) were used and time-dependent sensitization (TDS) was used as the experimental model of PTSD. Standardized WS root extract (100 and 300 mg/kg, p.o. for 15 days) was administered with TDS and their effects were observed on neurobehavioral (anxiety) and brain cytokines, corticosterone, and oxidative stress markers. Exposure to TDS resulted in anxiogenic behavior in the elevated plus maze (EPM) test, i.e., reductions in open arm entries and open arm time, as compared to the control group. Pretreatment with WS extract (100 and 300 mg/kg × 14 days) attenuated the TDS-induced anxiogenic activity in a dose-related manner, and these WS effects were comparable to those seen after the comparator drug fluoxetine (10 mg/kg). Assay of brain homogenates showed that TDS also resulted in elevations in brain interleukin-6 and reduction in corticosterone levels in both the hippocampus and prefrontal cortex (PFC), which were reversed after WS pretreatments. Further, WS pretreatment also reversed the TDS-induced changes in brain oxidative stress markers, namely elevated malondialdehyde and reduced glutathione levels in both the hippocampus and PFC. These results suggest that WS could have potential as a therapeutic agent for treating PTSD by attenuating anxiogenesis, neuroimmune axis activation, and oxidative stress.