INVIVO TRAPPING OF HYDROXYL FREE-RADICALS IN THE STRIATUM UTILIZING INTRACRANIAL MICRODIALYSIS PERFUSION OF SALICYLATE - EFFECTS OF MPTP, MPDP+, AND MPP+

Increased formation of hydroxyl free radicals (. OH) reflected by . OH adduct of salicylate in brain dialysate was demonstrated during the sustained (more than 2 hours) dopamine overflow elicited by 75 nmol of 1-methyl-4-phenyldihydropyridine (MPDP+) and 1-methyl-4-phenylpyridinium (MPP+) in the rat striatum. Owing to its weak dopamine releasing action, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) did not significantly increase the . OH formation. This data suggests that sustained elevation of dopamine in the extracellular fluid elicited by MPTP analogues can be auto-oxidized, which in turn leads (possibly by indirect mechanisms) to the formation of cytotoxic .OH free radicals near the nigrostriatal terminals.