The effect of NMDA antagonists in the radial arm maze task with an interposed delay

Abstract

N-Methyl-d-aspartate (NMDA) receptors mediate the triggering of hippocampal long-term potentiation (LTP), a current physiological model of memory. This model was tested in the rat through the effect of (+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5, 10-imine maleate (MK-801, a novel noncompetitive NMDA antagonist) on the radial arm maze (RAM) task with a 15-minute delay interposed at the midpoint choice. In two separate experiments, substereotypical drug doses of MK-801 and phencyclidine (a dissociative anesthetic with NMDA antagonist properties) were given intraperitoneally, before the trial or at the start of the delay. “Efficiency” was impaired in both tasks, but near-instantaneous use of encoded information seemed to be unaffected. This evidence would support a proposed role for NMDA-mediated pathways (and possibly LTP) in delayed stages of memory formation or use.