Ebselen attenuates reserpine-induced orofacial dyskinesia and oxidative stress in rat striatum

Reserpine-induced orofacial dyskinesia is an alleged animal model of tardive dyskinesia whose pathophysiology has been related to striatal oxidative stress. In the present investigation, the authors examined whether ebselen, an antioxidant organochalcogen with glutathione peroxidase-like activity, changes the behavioral and neurochemical effect of acute reserpine administration. Reserpine injection for 3 days every other day caused a significant increase on the tongue protrusion frequency and ebselen (30 mg/kg ip for 4 days, starting I day before reserpine) reversed partially the effect of reserpine (P<.05). Reserpine- and reserpine + ebselen-treated groups displayed an increase in vacuous chewing frequency when compared to control and ebselen-treated groups (P<.05) Reserpine increased the duration of facial twitching and ebselen reversed partially the effect of reserpine (P<.01). Reserpine increased significantly the thiobarbituric acid-reactive species (TBARS) levels, and ebselen reversed the effect of reserpine on TBARS production in rat striatum. The results of the present study clearly indicated that ebselen has a protective role against reserpine-induced orofacial dyskinesia and reversed the increase in TBARS production caused by reserpine administration. Consequently, the use of ebselen as a therapeutic agent for the treatment of tardive dyskinesia should be considered. (C) 2002 Elsevier Science Inc. All rights reserved.