Blockers of NMDA‐operated channels decrease glutamate and aspartate extracellular accumulation in striatum during forebrain ischaemia in rats

Summary— Brain microdialysis was used to study changes in the glutamate and aspartate extracellular concentrations in the striatum of conscious rats submitted to 30 minutes cerebral ischaemia, using the four‐vessel occlusion model. Perfusion of the N‐methyl‐D‐aspartate (NMDA) receptor channel blockers, dizocilpine (MK‐801; 75 μM) and Mg²⁺ (2.5 mM), inhibited the ischaemia‐induced accumulation of glutamate and aspartate. The AMPA/kainate receptor antagonist, 2,3‐dihydroxy‐6‐nitro‐7‐sulfamylbenzo (F) quinoxaline (NBQX; 15 μM and 450 μM) had no effect on glutamate and aspartate levels during ischaemia. On the other hand, omission of Ca²⁺ from the perfusing solution did not alter the increases in glutamate and aspartate induced by ischaemia. These results suggest that the glutamate and aspartate accumulation in four‐vessel occlusion ischaemia is mediated by activation of NMDA receptors in a Ca²⁺ independent manner. 1995 Société Française de Pharmacologie et de Thérapeutique