Local striatal infusion of MPP+ does not result in increased hydroxylationafter systemic administration of 4-hydroxybenzoate

In vivo bilateral microdialysis in the rat striatum was used to investigate hydroxyl radical formation under basal conditions and after intrastriatal administration of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). After a short equilibration period, 4-hydroxybenzoate (4HBZ), which scavenges hy droxyl radicals to produce 3,4-dihydroxy-benzoate (34DHB), was injected int raperitoneally 15 min before infusion of MPP+. To evaluate the enzymatic co ntribution to hydroxyl radical formation, two other series of microdialyses were performed following administration of monoamine oxidase B inhibitors, either l-deprenyl (selegiline) or MDL 72,974A [(E)-2-(4-fluorophenethyl)-3 -fluoroallylamine hydrochloride]. Microdialysate samples were analyzed by h igh-performance liquid chromatography for catecholamines, 3,4-dihydroxyphen ylacetate (DOPAC), homovanillate (HVA), along with the hydroxyl radical add uct, 34DHB and its precursor, 4HBZ. MPP+ administration resulted in a massi ve release of dopamine along with a decrease in DOPAC and HVA in all three groups. A striking effect in all three groups was noted in which MPP+ resul ted in a decrease in interstitial 4HBZ to <50% of the non-MPP+-treated side . In absolute terms, the amount of 34DHB produced was low but similar in al l three groups, even after unilateral MPP+ infusion. When 34DHB was normali zed to 4HBZ release to account for differences in precursor availability, t here were no significant differences in the 34DHB/4HBZ ratios either with o r without MAO inhibitor treatment or after local MPP+ infusion. Systemic 4H BZ administration appears to result predominantly in intra-cellular samplin g of hydroxyl radicals which produces different results from local infusion of trapping agents such as salicylate. (C) 1999 Elsevier Science Inc.