NMDA RECEPTOR ANTAGONISTS INHIBIT CATALEPSY INDUCED BY EITHER DOPAMINE-D1 OR DOPAMINE-D2 RECEPTOR ANTAGONISTS

In the present study, we investigated the ability of NMDA receptor ant agonists to inhibit catalepsy induced by haloperidol. or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respecti vely. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatmen t with either the non-competitive NMDA receptor antagonist, MK-801 (0. 25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/k g i.p.) reduced the cataleptic response produced by haloperidol (1.0 m g/kg). SCH23390 (2.5-10 mg/kg i.p.) or clebopride (5-20 mg/kg i.p.). T his demonstrates that NMDA receptor antagonists will reduce both dopam ine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant d oses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the cataleps y induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. T hese results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic f unction, such as Parkinson's disease.