AMELIORATION OF SOME NEUROLEPTIC-INDUCED DEFICITS BY THE NMDA ANTAGONIST MK-801 IN A CONDITIONED REACTION-TIME-TASK

Using a reaction time task sensitive to neuroleptic disruption, we have examined the ability of the non-competitive NMDA antagonist MK-801 (0.01-0.16 mg/kg) to reverse impairments induced by chlorpromazine (2.0 mg/kg). Rats were required to depress a lever for a randomly determined duration, and release it within 1 sec of a light cue in order to obtain food reward. Chlorpromazine reduced the overall number of lever presses, caused an early cessation of responding, slowed lever release in response to an external cue, and increased the time taken to reach the food hopper after a correct response. MK-801 differentially influenced these impairments, with no dose of drug completely normalising behaviour. The reduction in response levels and early termination of responding were partially reversed by MK-801, whilst certain doses of the drug completely reversed the increased time taken to reach the food hopper. Although MK-801 increased the likelihood that chlorpromazine-treated rats would release the lever within the 1 sec criterion time to obtain reinforcement, reaction times with the drug combination were still slower than observed in the control session. Therefore, MK-801 appears to be less effective in reversing the chlorpromazine-induced deficit in movement initiation than certain other aspects of performance in this task. These findings are less promising than those from other studies which have been used to suggest a clinical use of NMDA antagonists in the treatment or idiopathic and neuroleptic-induced parkinsonism.