Potentiation by Kainate of Excitatory Amino Acid Release in Striatum: Complementary In Vivo and In Vitro Experiments

Abstract

The effect of kainate on extracellular levels of amino acids in corpus striatum was investigated in vitro and in vivo, to elucidate the mechanism underlying its neurotoxicity. Kainate increased extracellular glutamate and aspartate in both striatal slices in vitro and intact striatum in vivo, as previously reported. Both in vitro and in vivo, DL-threo-3-hydroxyaspartate increased extracellular glutamate and aspartate levels (to between 150 and 200% of basal), and also enhanced their kainate-evoked release. The action of kainate in vivo was reduced by prior frontal decortication, whereas in vitro the kainate-evoked responses were only slightly reduced by tetrodotoxin, and remained above control values. These results confirm that kainate increases extracellular glutamate and aspartate, and provide evidence that this is due to synaptic release evoked by an action on receptors on glutamatergic neurone terminals. These findings may be relevant to the understanding of epilepsy.