EFFECTS OF A GLUTAMATE UPTAKE INHIBITOR ON GLUTAMATE RELEASE INDUCED BY VERATRIDINE AND ISCHEMIA

It has been postulated that a reversal of glutamate reuptake (''uptake reverse'') may contribute to glutamate release during cerebral ischem ia. We tested this hypothesis by studying the effect of threo-3-hydrox y-DL-aspartic acid (THA), a glutamate uptake inhibitor, on extracellul ar glutamate accumulation measured by microdialysis during ii-vessel i schemia (20 min). The inhibitory effect of THA on sodium-dependent glu tamate uptake was measured in vitro on rat hippocampal slices (K-i = 4 5 +/- 11 mu M). We examined in vivo the effect of THA (400 mu M in the dialysis solution) on the extracellular glutamate release from the ra t hippocampus, during veratridine depolarization and ischemia. THA dec reased the amount of glutamate appearing in the extracellular space du ring veratridine depolarization (61%). In contrast, the glutamate rele ase induced by ischemia was nor affected by THA. We conclude that a re versal of the sodium-dependent uptake contributes to an increase in ex tracellular glutamate during veratridine depolarization. In contrast, glutamate release occurring during ischemia is not mediated by uptake reverse.