Effect of Withania somnifera Root Extract on Haloperidol-Induced Orofacial Dyskinesia: Possible Mechanisms of Action

Abstract

We investigated the role of oxidative stress in the pathophysiology of haloperidol (HP)-induced orofacial dyskinesia and evaluated the beneficial effect of Withania somnifera (Ws) root extract in the amelioration of HP-induced vacuous chewing movements (VCMs) and tongue protrusions in the rat model for TD. Rats were treated for 21 days with intraperitoneal HP (1 mg/kg); on day 22, VCMs and tongue protrusions were counted during a 5-minute observation period. HP-treated rats significantly developed these extrapyramidal symptoms, but coadministration of Ws root extract (100-300 mg/kg) dose-dependently reduced them. Biochemical analysis revealed that chronic HP treatment significantly increased lipid peroxidation and decreased forebrain levels of glutathione and the antioxidant defense enzymes, superoxide dismutase (SOD) and catalase. Coadministration of Ws extract significantly reduced the lipid peroxidation and significantly reversed the decrease in forebrain SOD and catalase levels but had no significant effect on the HP-induced decrease in forebrain glutathione levels. These findings strongly suggest that oxidative stress plays a significant role in HP-induced orofacial dyskinesia and that Ws could be effective in preventing neuroleptic-induced extrapyramidal side effects.