Testing hypotheses of spatial learning: the role of NMDA receptors and NMDA-mediated long-term potentiation

Behav Brain Res. 1997 Mar;84(1-2):179-93. doi: 10.1016/s0166-4328(96)00149-0.

Abstract

The role of NMDA receptors and NMDA-mediated hippocampal long-term potentiation (LTP) in spatial learning was studied in rats using the competitive, systemically administered NMDA receptor antagonists CGS19755 ((+/-)-cis-4-phosphonomethyl-2-piperidine carboxylic acid) and NPC17742 (2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid). CGS19755 caused sensorimotor disturbances and disrupted acquisition of the water maze in naive rats. The sensorimotor disturbances were greatly reduced and maze learning was normal in spite of the blockade of dentate gyrus LTP by CGS19755 in rats that had first been familiarized with the general task requirements by non-spatial pretraining. In a second experiment, antagonism of NMDA receptors caused small, but reliable, impairments in Y-maze and visible platform visual discrimination tasks. The results indicate that NMDA receptors are not crucial for water maze acquisition using a spatial learning strategy, and that NMDA antagonists cause visual and other sensorimotor disturbances in naive rats that could help account for their poor performance in this task.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Learning / drug effects
  • Learning / physiology*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • N-Methylaspartate / physiology*
  • Pipecolic Acids / pharmacology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Space Perception / drug effects
  • Space Perception / physiology*

Substances

  • Amino Acids
  • Excitatory Amino Acid Antagonists
  • Pipecolic Acids
  • Receptors, N-Methyl-D-Aspartate
  • NPC 12626
  • selfotel
  • N-Methylaspartate