Posttraining Injections of MK-801 Produce a Time-Dependent Impairment of Memory in Two Water Maze Tasks

The role of glutamatergicN-methyl-d-aspartate (NMDA) receptors in memory storage processes was examined using systemic posttraining injections of MK-801. Male Long–Evans rats received an eight-trial (30-s ITI) training session on a spatial or cued water maze task. In the spatial task, a submerged escape platform was located in the same quadrant of the maze on all trials. In the cued task, a visible escape platform was located in a different quadrant of the maze on each trial. Following Trial 8 in both tasks, the rats received a posttraining intraperitoneal injection of the NMDA receptor antagonist MK-801 (0.025, 0.05, 0.1, or 0.2 mg/kg) or saline. On a retention test session 24 h later, latency to mount the escape platform was used as a measure of memory. In both tasks, the retention test escape latencies of animals given MK-801 (0.05 and 0.1 mg/kg) were significantly higher than those of saline-injected controls, indicating a drug-induced impairment of memory. Injections of MK-801 (0.05 mg/kg) did not affect retention when administered 2 h posttraining in either task, indicating that the effects of MK-801 on retention are not due to an influence on non-mnemonic factors. Control experiments indicated that the memory impairing effects of MK-801 were due to an influence on memory for the type of discrimination training given (i.e., spatial or cued) and not due to an influence on a mnemonic strategy common to both tasks. The findings indicate a time-dependent role for NMDA receptor function in memory storage processes.