A novel NMDA antagonist, MK-801, impairs performance in a hippocampal-dependent spatial learning task.

N-Methyl-d-aspartate (NMDA) receptors have been implicated with the triggering of long-term potentiation, a currently studied physiological model of learning and memory. The compound (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801) has recently been classified as a potent and selective NMDA antagonist acting at the associated ion channel. After determination of the highest intraperitoneal dose of MK-801 at which increases in activity (measured in photocell activity cages and 3-arm maze) were not observed (0.2 mg/kg), rats that had been previously trained to obtain food pellets in an 8-arm radial maze up to criterion were tested with 0.1 and 0.2 mg/kg doses. Dose-related decreases in "efficiency" in the task were found. The present findings support the suggestion that NMDA antagonists cause impairments in "working memory" and also support the status of long-term potentiation as a physiological model of memory.