MPTP TOXICITY IN RAT STRIATAL SLICES - DOPAMINE UPTAKE ALTERATION DOES NOT APPEAR TO BE RELATED TO LIPID-PEROXIDATION

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is used to create experimental models of parkinsonism, induces both dopaminergic neurotoxicity and peroxidation reactions. The present work investigate d the interaction between the dopamine (DA) uptake system, lipid perox idation and MPTP in a rat striatum slice model. [H-3]DA uptake was dec reased and the concentration of thiobarbituric acid reactive substance s (TEARS) increased after a plain preincubation in Krebs-Ringer bicarb onate buffer for 150 min. The decrease in [H-3]DA uptake and the incre ase in TEARS were suppressed by the iron-chelating agent desferrioxami ne. Inhibition of [H-3]DA uptake was intensified, [H-3]GBR 12935 bindi ng to DA uptake sites was decreased and TEARS production was inhibited in slices after preincubation with MPTP. MPTP effects were inhibited by L-deprenyl, a MAO-B inhibitor. These results suggest that the spont aneous decrease in DA uptake during simple preincubation in pure Krebs -Ringer solution was related to spontaneous TEARS generation. During M PTP preincubation, alteration of the DA uptake mechanism was not due t o additional lipid peroxidation since TEARS production was decreased. MPTP effects could have resulted from other events which are discussed . (C) 1997 Elsevier Science Ireland Ltd.