Enhanced N-methyl-D-aspartate function reverses working memory failure induced by blockade of group I metabotropic glutamate receptors in the rat hippocampus.

Intrahippocampal administration of (R,S)-1-aminoindan-1, 5-dicarboxylic acid (AIDA), a potent and selective antagonist of the group I metabotropic glutamate receptor (mGluR), at doses of 0.32-3.2 microg/side dose-dependently increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup. The increase in working memory errors induced by intrahippocampal 3.2 microg/side AIDA was significantly reduced by concurrent infusion of 10 microg/side D-cycloserine, a partial agonist at the glycine binding site on the N-methyl-D-aspartate (NMDA) receptor/channel complex. These results suggest that positive modulation of the NMDA receptor/ channel through activation of the glycine site can compensate for deficiency of hippocampal group I mGluR-mediated neurotransmission involved in working memory function.