Differential role of dopamine D-1 and D-2 receptors in isoniazid-induced vacuous chewing movements

Tardive dyskinesia (TD) is a syndrome of potentially irreversible and invol untary hyperkinetic disorders that occurs during chronic neuroleptic therap y and is a major limitation of such therapy. Vacuous chewing movements (VCM s) in rats have been widely accepted as an animal model of tardive dyskines ia. In the present study isoniazid (1, 2 and 5 muM i.c.v.) dose-dependently produced VCMs in rats. The response produced by a 10-muM dose was lower th an that of earlier doses but was statistically significant when compared to a saline-treated group. Diazepam (1 and 4 mg/kg i.p.) and progabide (50 an d 100 mg/kg i.p.) dose-dependent reversed the isoniazid-induced VCMs. Halop eridol (0.5 and 1 mg/kg i.p.) and SCH-23390 (0.25 and 0.5 mg/kg i.p.) rever sed the isoniazid-induced VCMs in a dose-dependent manner. Sulpiride (25 an d 50 mg/kg i.p.) a dopamine D-2 receptor antagonist, had no effect on isoni azid-induced VCMs, SKF-38393 (10 and 15 mg/kg i.p.) dose-dependently augmen ted the isoniazid-induced VCMs. Quinpirole 0.02 mg/kg i.p. had no effect on isomiazid-induced VCMs but a higher quinpirole dose (0.05 mg/kg) significa ntly reduced isoniazid-induced VCMs. Isoniazid (2 muM i.c.v.) produced ster eotypy (grooming and rearing) in rats. Haloperidol (0.5 and 1 mg/kg i.p.). SCH-23390 (0.25 and 0.5 mg/kg i.p.) and sulpiride (25 and 50 mg/kg i.p.) de creased the severity of isoniazid-induced stereotypy. SKF-38393 (10 and 15 mg/kg i.p.) dose-dependently augmented the isoniazid-induced grooming behav ior more prominently as compared to quinpirole (0.02 and 0.05 mg/kg i.p.): on the other hand quinpirole potentiated isoniazid-induced rearing behavior . In conclusion, the results of the present study demonstrated the differen tial involvement of dopamine D-1 and D-2 receptors in isoniazid-induced VCM s. (C) 2000 Prous Science. All rights reserved.