POSTTRAINING INJECTIONS OF MK-801 PRODUCE A TIME-DEPENDENT IMPAIRMENTOF MEMORY IN 2 WATER MAZE TASKS

The role of glutamatergic N-methyl-D-aspartate (NMDA) receptors in mem ory storage processes was examined using systemic posttraining injecti ons 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 w as located in a different quadrant of the maze on each trial. Followin g Trial 8 in both tasks, the rats received a posttraining intraperiton eal 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, lat ency to mount the escape platform was used as a measure of memory. In both tasks, the retention test escape latencies of animals given MX-80 1 (0.05 and 0.1 mg/kg) were significantly higher than those of saline- injected controls, indicating a drug-induced impairment of memory. Inj ections of MK-801 (0.05 mg/kg) did not affect retention when administe red 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 tim e-dependent role for NMDA receptor function in memory storage processe s. (C) 1997 Academic Press.