Antagonism of metabotropic glutamate receptor 4 receptors by (RS)-alpha-cyclopropyl-4-phosphonophenylglycine alters the taste of amino acids in rats

Neuroscience. 2009 Nov 10;163(4):1292-301. doi: 10.1016/j.neuroscience.2009.07.035. Epub 2009 Jul 22.


T1R1/T1R3, taste-metabotropic glutamate receptor (mGluR) 4 and other taste receptors have been implicated in umami taste perceptionT1R1/T1R3 has also been identified as an L-amino acid receptor. We investigated the possibility that taste-mGluR4 receptors may also play a role in the taste of amino acids in Sprague-Dawley rats using conditioned taste aversion methods. Specifically, we examined whether a taste aversion generalized between L-monosodium glutamate (MSG) and one of three amino acids (glycine, L-serine, and L-arginine), and whether (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG), a group III mGluR selective antagonist with a strong binding affinity for mGluR4 receptors, can impact stimulus generalization. Rats showed cross-generalization between MSG and all three amino acids (all mixed with amiloride to block the taste of sodium), although less so for L-arginine than the other two amino acids, suggesting that all of the amino acids shared at least some taste qualities with MSG. However, when 1 mM CPPG was mixed with these amino acids, the strength of the learned taste aversions and cross-generalization for all but glycine were either decreased or increased. The increase in generalization induced by CPPG indicated that the antagonist did not simply reduce the intensity of the stimulus experience but also changed the qualities of the sensory experience. These findings suggest that multiple receptors are involved in amino acid taste and that taste-mGluR4 receptors contribute to the taste of MSG and at least some l-amino acids.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids*
  • Animals
  • Arginine
  • Avoidance Learning
  • Conditioning, Classical
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Male
  • Neuropsychological Tests
  • Physical Stimulation
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Serine
  • Sodium Glutamate
  • Taste Perception / drug effects*
  • Taste Perception / physiology


  • Amino Acids
  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • cyclopropyl-4-phosphonophenylglycine
  • Serine
  • Arginine
  • Glycine
  • Sodium Glutamate
  • metabotropic glutamate receptor 4