LACK OF INVOLVEMENT OF GLUTAMATE-INDUCED EXCITOTOXICITY IN MPP- POSSIBLE INVOLVEMENT OF ASCORBATE( TOXICITY IN STRIATAL DOPAMINERGIC TERMINALS )

1 The present study concerns the possible relationship between glutama te excitotoxicity and 3,6-tetrahydropyridine/1-methyl-4-phenylpyridini um (MPTP/MPP+) neurotoxicity on striatal dopaminergic terminals. 2 MPP + neurotoxicity has been studied by means of two MPP+ perfusions separ ated by 24 h. After the second MPP+ 1 mM perfusion, dopamine extracell ular output, measured by microdialysis, was considered to be an index of the dopaminergic neurone damage produced by the first MPP- 1 mM per fusion. 3 High concentration (10 mM) of glutamate uptake inhibitor L-t rans-pyrrolidine-2,4-dicarboxylic acid (PDC) stimulated basal release of dopamine and protected against the neurotoxic effect of MPP+. 4 PDC 10 mM perfusion produced an increase in the extracellular output of g lutamate and aspartate, and a decrease in that of ascorbate. 5 The pro tective effect against MPP+ toxicity observed with PDC 10 mM was compl etely abolished when this glutamate uptake inhibitor was co-perfused w ith ascorbate 0.5 mM. 6 These results suggest that glutamate-induced n eurotoxicity is not involved in MPP+ toxicity. The protective effect f ound with the glutamate uptake inhibitor could be due to a decrease in extracellular ascorbate levels.