An α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Antagonist and an N-Methyl-D-aspartate (NMDA) Channel Blocker Synergistically Impair Spatial Memory in Rats

Abstract

The interaction of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist YM90K with the competitive N-methyl-D-aspartate (NMDA) antagonist CGS19755 or with the NMDA channel blocker MK801 on the spatial memory of rats was examined by the 4-arm-baited radial maze task. When administered alone, these drugs had no effect on the spatial memory. The combination YM90K and MK801 synergistically disrupted working and reference memories, whereas the combination of YM90K and CGS19755 had no effect. These results indicate that the blockade of the AMPA recepor and NMDA channels produces a synergistic impairment of spatial memory and suggest that interaction between the AMPA and NMDA receptors plays a role in congnitive function.