NMDA antagonists produce site-selective impairment of accuracy in a delayed nonmatch-to-sample task in rats

Antagonists at the N-methyl-D-aspartate (NMDA) sub-type of glutamate receptor are purported to have detrimental effects on cognitive processes. In order to examine the site selectivity of these effects, phencycline (PCP), dizocilpine, and memantine (PCP-site antagonists), SDZEAA 494 and NPC17742 (competitive NMDA antagonists), ACEA 1021 (glycine-site antagonist), and eliprodil (NR2B-selective polyamine-site selective antagonist) were tested in rats performing a delayed nonmatch-to-sample task. Dizocilpine, PCP and memantine significantly decreased accuracy and discriminability, particularly during brief delay trials. In contrast, the competitive NMDA antagonists, SDZ EAA 494 and NPC 17742, did not affect accuracy or discriminability at any delay. Similarly, ACEA 1021, and eliprodil did not alter behavioral indices in a manner suggesting compromise in information processing at any delay even at doses that decreased the total number of trials completed. These data support previous findings that the effects of NMDA antagonists on accuracy are site-selective, with PCP-site antagonists producing the greatest disruption. Further, while not conclusive, the results are consistent with the hypothesis that NMDA receptor-mediated neurotransmission may be important at early stages of information processing, although further research is necessary to confirm these latter observations.