NMDA but not AMPA receptor antagonists impair the delay-interposed radial maze performance of rats

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonists CGS19755 and MK801 and the 2-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptor antagonist YM90K on spatial working memory were investigated by using a delay-interposed radial-arm maze (RAM) task in rats. CGS19755 and MK801, at the largest dose that had no effect on the performance in the nondelayed RAM task, significantly decreased the initial correct response after the 5-min delay in the delay-interposed RAM task. In contrast, YM90K had no effect on the initial correct response and arm reentries in both the delay-interposed and nondelayed RAM task. CGS19755, MK801 and YM90K, at all doses tested, did not alter the running time in either the delayed or the nondelayed RAM tasks. These results suggest that spatial working memory can be impaired by a blockade of NMDA receptor function and that such impairment is particularly sensitive to delay interposition. The lack of effect of the AMPA receptor antagonist provides additional evidence of the importance of the NMDA subtype of the glutamate receptors in cognitive processes.