TESTING HYPOTHESES OF SPATIAL-LEARNING - THE ROLE OF NMDA RECEPTORS AND NMDA-MEDIATED LONG-TERM POTENTIATION

The role of NMDA receptors and NMDA-mediated hippocampal long-term pot entiation (LTP) in spatial learning was studied in rats using the comp etitive, systemically administered NMDA receptor antagonists CGS19755 ((+/-)-cis-4-phosphonomethyl-2-piperidine carboxylic acid) and NPC1774 2 -2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid). CGS19755 c aused sensorimotor disturbances and disrupted acquisition of the water maze in naive rats. The sensorimotor disturbances were greatly reduce d and maze learning was normal in spite of the blockade of dentate gyr us LTP by CGS19755 in rats that had first been familiarized with the g eneral task requirements by non-spatial pretraining. In a second exper iment, antagonism of NMDA receptors caused small, but reliable, impair ments in Y-maze and visible platform visual discrimination tasks. The results indicate that NMDA receptors are not crucial for water maze ac quisition using a spatial learning strategy, and that NMDA antagonists cause visual and other sensorimotor disturbances in naive rats that c ould help account for their poor performance in this task.