Post-acquisition hippocampal NMDA receptor blockade sustains retention of spatial reference memory in Morris water maze

Abstract

Several studies have demonstrated that the hippocampal N-methyl-d-aspartate type glutamate receptors (NMDARs) are necessary for the acquisition but not the retention of spatial reference memory. In contrast, a few studies have shown that post-acquisition repetitive intraperitoneal injections of an NMDAR antagonist facilitate the retention of spatial reference memory in a radial maze task. In the present study, we investigated the role of hippocampal NMDARs in the retention of spatial reference memories in Morris water maze. In Experiment 1, 24h after training (4 trials/day for 4 days), d-AP5 was chronically infused into the hippocampus of rats for 5 days. In the subsequent probe test (seven days after training), we found that rats infused with d-AP5 spent a significantly longer time in the target quadrant compared to chance level, whereas rats in the control group did not. In Experiment 2, d-AP5 was infused into the hippocampus 1 (immediate) or 7 (delayed) days after the training session. In the probe test, following the retention interval of 13 days, immediate infusion facilitated the performance in a manner similar to Experiment 1, whereas the delayed infusion did not. These findings suggest that hippocampal NMDARs play an important role in the deterioration of spatial reference memory.