Behavioral effects of MK-801 mimic deficits associated with hippocampal damage

This study was undertaken to assess the behavioral effects of MK-801 [(+)5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclo-hepten-5,10-imine maleate], an anticonvulsant that binds to thereby blocks N-methyl-D-aspartate (NMDA) fonction. Such compounds prevent long-term potentiation (LTP) in the hippocampus and provide an important tool for assessing whether animals depend on LTP for learning. The results of the present experiments indicate that MK-801 administration impairs acquisition of some forms of learning (i.e., spatial learning and taste potentiation of an acquired odor aversion) that are normally dependent on the integrity of the hippocampal formation. In a narrow dose range, deficits were obtained on these tasks while other measures of learning/performance (i.e., cue learning in the same maze as was used for assessment of spatial learning, and simple associations formed between either a taste or odor stimulus paired with an effective unconditioned stimulus) were spared. These results are consistent with the view that an NMDA mechanism is critical for certain forms of learning, and that the effects of MK-801 mimic deficits produced by hippocampal damage.