Allosteric enhancement of metabotropic glutamate receptor 5 function promotes spatial memory

Neuroscience. 2006 Oct 27;142(3):691-702. doi: 10.1016/j.neuroscience.2006.06.043. Epub 2006 Aug 4.

Abstract

Group I metabotropic glutamate receptors (mGluRs) have been implicated in learning and memory formation. Recent findings indicate an important function of the group I mGluR subtype 5. Here, we used the Y-maze spatial alternation task and examined whether enhancement of intrinsic mGluR5 activity immediately after learning, i.e. during a critical period for memory consolidation, would have any consequences on long-term memory retention in rats. Intracerebroventricular application of the allosteric mGluR5 potentiator DFB (3,3'-difluorobenzaldazine) resulted in a marked improvement in spatial alternation retention when it was tested 24 h after training. The promnesic effect increased with the difficulty of the task and was apparently due to a substantial enhancement of consolidation. The applied dose of DFB did not cause behavioral changes in the open field, and was devoid of structural side-effects as evaluated by immunohistochemical examination. Our results suggest an important function of post-training mGluR5 activation in some types of hippocampus-dependent spatial learning.

Publication types

  • Comparative Study

MeSH terms

  • Allosteric Regulation / drug effects
  • Animals
  • Behavior, Animal / drug effects
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Hydrazines / pharmacology
  • Immunohistochemistry / methods
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Memory / physiology*
  • Nerve Tissue Proteins / metabolism
  • Parvalbumins / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*
  • Spatial Behavior / drug effects
  • Spatial Behavior / physiology*
  • Statistics, Nonparametric
  • Time Factors

Substances

  • 3,3'-difluorobenzaldazine
  • Grm5 protein, rat
  • Hydrazines
  • Nerve Tissue Proteins
  • Parvalbumins
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate