DISTINCT COMPONENTS OF SPATIAL-LEARNING REVEALED BY PRIOR TRAINING AND NMDA RECEPTOR BLOCKADE

SYNAPTIC plasticity dependent on N-methyl-D-aspartate (NMDA) receptors is thought to underlie certain types of learning and memory(1 3). In support of this, both hippocampal long-term potentiation and spatial l earning in a watermaze are impaired by blocking NMDA receptors with a selective antagonist D(-)-2-amino-5-phosphonovaleric acid (AP5)(4) or by a mutation in one of the receptor subunits(5). Here we report, howe ver, that the AP5-induced learning deficit can be almost completely pr evented if rats are pretrained in a different watermaze before adminis tration of the drug. This is not because of stimulus generalization, a nd occurs despite learning of the second task remaining hippocampus de pendent. An APS-induced learning deficit is, however, still seen if th e animals are pretrained using a non-spatial task. Thus, despite its p rocedural simplicity, the watermaze may involve multiple cognitive pro cesses with distinct pharmacological properties; although required for some component of spatial learning, NMDA receptors may not be require d for encoding the spatial representation of a specific environment.