MK801, an NMDA antagonist, blocks acquisition of a spatial task but does not block maternal experience effects.

Two studies were conducted to determine the effect on learning and memory of MK801, an N-methyl-D-aspartate (NMDA) antagonist that acts through noncompetitive blockade of the ion channel associated with the NMDA receptor. In the first study we found a dose-dependent impairment in the acquisition of a modified radial-arm maze task, resulting from injections (IP) of MK801 10 minutes prior to training. The retention of that learning, as measured by the amount of training required for reacquisition on the following day, was unaffected by the drug. In contrast, in the second study, MK801 did not block the experience-based facilitation of maternal responding seen 8 days after one hour of exposure to pups: experienced dams showed facilitated onset of maternal behavior, relative to inexperienced dams, regardless of the drug they received. However, injections of MK-801, either just before or just after the maternal experience, did lead to some deficits in maternal responding on the first day of testing. We have previously shown that these maternal experience effects are blocked by injections (ICV, SC) of cycloheximide, a protein synthesis inhibitor. These results suggest that the NMDA system does not mediate all, if any, of cycloheximide's effects on maternal experience and, furthermore, that the NMDA system may mediate some but not all forms of learning.