Distinct components of spatial learning revealed by prior training and NMDA receptor blockade

Nature. 1995 Nov 9;378(6553):182-6. doi: 10.1038/378182a0.


Synaptic plasticity dependent on N-methyl-D-aspartate (NMDA) receptors is thought to underlie certain types of learning and memory. In support of this, both hippocampal long-term potentiation and spatial learning in a watermaze are impaired by blocking NMDA receptors with a selective antagonist D(-)-2-amino-5-phosphonovaleric acid (AP5) or by a mutation in one of the receptor subunits. Here we report, however, that the AP5-induced learning deficit can be almost completely prevented if rats are pretrained in a different watermaze before administration of the drug. This is not because of stimulus generalization, and occurs despite learning of the second task remaining hippocampus dependent. An AP5-induced learning deficit is, however, still seen if the animals are pretrained using a non-spatial task. Thus, despite its procedural simplicity, the watermaze may involve multiple cognitive processes with distinct pharmacological properties; although required for some component of spatial learning, NMDA receptors may not be required for encoding the spatial representation of a specific environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Cerebrospinal Fluid
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hippocampus / physiology
  • Long-Term Potentiation
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology*
  • Memory / drug effects
  • Memory / physiology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Space Perception / physiology*


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • 2-Amino-5-phosphonovalerate