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.
Li
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Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Japan.
Matsumoto
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Yamamoto
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Watanabe
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D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects*; D010875:Pipecolic Acids / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013028:Space Perception / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C086162:6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione; C053672:selfotel; D016291:Dizocilpine Maleate