Effect of Withania somnifera root extract on reserpine-induced orofacial dyskinesia and cognitive dysfunction

Tardive dyskinesia is one of the major side effects of long-term neuroleptic treatment. The pathophysiology of this disabling and commonly irreversible movement disorder is still obscure. Vacuous chewing movements in rats are widely accepted as an animal model of tardive dyskinesia. Oxidative stress and products of lipid peroxidation are implicated in the pathophysiology of tardive dyskinesia. Repeated treatment with reserpine (1.0 mg/kg) on alternate days for a period of 5 days (days 1, 3 and 5) significantly induced vacuous chewing movements and tongue protrusions in rats. Chronic treatment with Withania somnifera root extract (Ws) for a period of 4 weeks to reserpine treated animals significantly and dose dependently (50 and 100 mg/kg) reduced the reserpine-induced vacuous chewing movements and tongue protrusions. Reserpine treated animals also showed poor retention of memory in the elevated plus maze task paradigm. Chronic Ws administration significantly reversed reserpine-induced retention deficits. Biochemical analysis revealed that chronic reserpine treatment significantly induced lipid peroxidation and decreased the glutathione (GSH) levels in the brains of rats. Chronic reserpine treated rats showed decreased levels of antioxidant defense enzymes, superoxide dismutase (SOD) and catalase. Chronic administration of Ws root extract dose dependently (50 and 100 mg/kg) and significantly reduced the lipid peroxidation and restored the decreased glutathione levels by chronic reserpine treatment. It also significantly reversed the reserpine-induced decrease in brain SOD and catalase levels in rats. The major findings of the present study indicate that oxidative stress might play an important role in the pathophysiology of reserpine-induced abnormal oral movements. In conclusion, Withania somnifera root extract could be a useful drug for the treatment of drug-induced dyskinesia.