Competitive NMDA receptor blockers reduce striatal glutamate accumulation in ischaemia

Our previous studies have shown that kynurenic acid, a broad-spectrum antagonist of excitatory amino acid receptors, depressed the ischaemia-induced accumulation of glutamate and aspartate in rat striatum. In the present experiments we examined the effect of two competitive N-methyl-D-aspartate (NMDA) receptor antagonists on striatal extracellular glutamate concentrations induced by a 30 min '4-vessel occlusion' ischaemia in rats. Local perfusion with 2-amino-5-phosphonovalerate (AP5; 300 microM) and with 2-amino-7-phosphonoheptanoate (AP7; 300 microM), using a microdialysis fibre markedly reduced the ischaemia-induced increase in glutamate concentrations. These results indicate that, during forebrain ischaemia the NMDA receptor type mediates glutamate and aspartate accumulation in rat striatum.