Metabotropic glutamate receptor subtype 5 antagonism in learning and memory

Eur J Pharmacol. 2010 Aug 10;639(1-3):17-25. doi: 10.1016/j.ejphar.2009.12.039. Epub 2010 Apr 2.


The role of the metabotropic glutamate receptor 5 (mGlu(5) receptor) in learning and memory and other behaviors are reviewed by examining the influence of selective antagonists and genetic knockout on performance. This receptor is involved in spatial learning, contextual fear conditioning, inhibitory avoidance, fear potentiated startle, and conditioned taste aversion. However, mGlu(5) receptor antagonists have proven to be ineffective in other learning tasks, such as the delayed-match-to-position test and a three-hole spatial learning task. Locomotion is often decreased by mGlu(5) receptor antagonists; and other behaviors such as social interaction and consummatory responses can also be affected. In mGlu(5) receptor knockout mice, performance in contextual fear conditioning and spatial water maze tasks is impaired. Although the available evidence is suggestive of an important contribution of mGlu(5) receptors to cognitive functions, further studies are needed, particularly those with in vivo evaluation of the role of mGlu(5) receptors in selective brain regions in different stages of memory formation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Learning / drug effects*
  • Learning / physiology
  • Locomotion / drug effects
  • Locomotion / physiology
  • Memory / drug effects*
  • Memory / physiology
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / metabolism


  • Excitatory Amino Acid Antagonists
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate