(R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) blocks spatial learning in rats and long-term potentiation in the dentate gyrus in vivo

Neurosci Lett. 1994 Feb 14;167(1-2):141-4. doi: 10.1016/0304-3940(94)91047-2.


Recently, it was demonstrated by the use of the competitive and selective antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) that metabotropic glutamate receptor (mGluR) activation is required to induce long-term potentiation (LTP) in the hippocampus. Accordingly, we investigated whether MCPG also inhibits spatial learning. Rats were trained on a spatial alternation task in a Y-maze with footshock reinforcement, and MCPG (0.0208 mg) was injected intracerebroventricularly prior to training and/or retention test. Animals injected pre-training are clearly impaired in retention, whereas preretention application was without effect. A state dependency could be excluded. Additionally, MCPG at the same concentration completely blocks a potentiation at perforant path/dentate gyrus synapses in vivo. These results strongly implicate a role of mGluRs in spatial learning and LTP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / administration & dosage
  • Benzoates / pharmacology*
  • Electroshock
  • Foot
  • Glycine / administration & dosage
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Hippocampus / drug effects*
  • Hippocampus / physiology*
  • Injections, Intraventricular
  • Learning / drug effects*
  • Long-Term Potentiation / drug effects*
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Reinforcement, Psychology
  • Retention, Psychology / drug effects
  • Spatial Behavior / drug effects*


  • Benzoates
  • Receptors, Metabotropic Glutamate
  • alpha-methyl-4-carboxyphenylglycine
  • Glycine