Involvement of hippocampal NMDA and AMPA receptors in acquisition, formation and retrieval of spatial memory in the Morris water maze.

Abstract

This study investigated the roles of hippocampal N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA) receptors in acquisition, consolidation and retrieval processes of spatial memory. Male Wistar rats with indwelling cannulae in the dorsal hippocampus received 4 training trials on the Morris water maze for consecutively 6 days. Rats received infusion of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5) or the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) into the hippocampus under one of the three schedules: 5 min prior to each daily training session, immediately after each daily training session or 5 min prior to the final testing trial. Pretraining intra-hippocampal infusion of 5.0 micrograms AP5 retarded acquisition. The same dose of AP5 given after training had little effect but a higher dose (10.0 micrograms) did slow down progress in the acquisition curve. Pretest infusion AP5 failed to affect memory retrieval. Pretraining intra-hippocampal infusion of 1.0 micrograms CNQX also impaired acquisition, but posttraining infusion of CNQX at 1.0 or 2.0 micrograms had no effect. However, pretest infusion of 1.0 micrograms CNQX markedly impaired retrieval of the already-formed spatial memory. These findings taken together suggest that acquisition in a spatial task involves hippocampal NMDA and AMPA receptors, consolidation of spatial memory involves NMDA receptors and retrieving such memory involves AMPA receptors.