The NMDA antagonist dizocilpine (MK-801) reverses haloperidol-induced movement initiation deficits

The present study shows that systemic dopamine receptor blockade impaired movement initiation of rats, trained in a simple reaction time task for rapid initiation of locomotion in response to a combined optic/acoustic cue. Reaction time, movement time and the accelerative force were recorded for each initiation of locomotion. Results indicate a dose-related increase of reaction time following systemic administration of haloperidol (0.1, 0.15, 0.3 mg/kg i.p.). Measures derived from resulting force-time patterns showed a haloperidol-induced decrease (0.15 mg/kg i.p.) of the mean rate of force development, indicating a decreased initial acceleration. These effects were reversed by systemic co-administration of dizocilpine (MK-801) (0.08 mg/kg i.p.), a selective non-competitive N-methyl-D-aspartate (NMDA) antagonist. The haloperidol-induced movement initiation deficits in this task are in part comparable to akinesia seen in Parkinson's disease and their reversal by dizocilpine has implications for the treatment of this disease.