GLUTAMATE-INDUCED OVEREXPRESSION OF NMDA RECEPTOR MESSENGER-RNAS AND PROTEIN TRIGGERED BY ACTIVATION OF AMPA KAINATE RECEPTORS IN RAT HIPPOCAMPUS FOLLOWING FOREBRAIN ISCHEMIA/

Severe forebrain ischemia induces a large increase in expression of NM DA receptor subunits in rat brain. One week after ischemia, levels of NMDA-R1 mRNAs in the CA1 pyramidal cells of hippocampus are 7 times hi gher than those observed in control rats. At 7 days postischemia, an e nhanced immunostaining of the NMDA-R1 subunit was observed in all hipp ocampal structures indicating that changes in mRNA levels are accompan ied by changes in receptor protein level. Riluzole, a potent inhibitor of glutamate release and CNQX, a selective AMPA/kainate antagonist, d rastically reduced the ischemia-induced expression of mRNAs for the th ree NMDA receptor subunits while D-AP5, a selective NMDA antagonist, h ad essentially no effect. Therefore ischemia-induced expression of NMD A receptor subunits is associated with glutamate release and proceeds via an AMPA/kainate pathway. These results together with those of othe r groups concerning ischemia effects on AMPA and GABA(A) receptor leve ls, suggest an important role of the induced expression of NMDA recept or subunits in the deleterious effects of ischemia.