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.
Ohno
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Watanabe
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003523:Cycloserine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D007189:Indans / Q000008:administration & dosage; D008297:Male; D008568:Memory / Q000187:drug effects*; D008845:Microinjections; D016202:N-Methylaspartate / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
C095756:1-aminoindan-1,5-dicarboxylic acid; D007189:Indans; D018094:Receptors, Metabotropic Glutamate; D016202:N-Methylaspartate; D003523:Cycloserine