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The present studies were aimed at investigating the possible roles of dopamine (DA) and iron in production of hydroxyl radicals ( · OH) in rat striatum after Mn 21 intoxication. For this purpose, DA depletions were assessed concomitant with in vivo 2,3-and 2,5-dihydroxybenzoic acid (DHBA) formation from the reaction of salicylate with · OH, of which 2,3-DHBA is a nonenzymatic adduct. Following intrastriatal Mn 21 injection, marked 2,3-DHBA increases were observed in a time-and dose-dependent fashion reaching maximum levels at 6-18 h and a plateau beyond 0.4 mmol

Regional 45Ca2+ accumulation and analysis of monoamines and metabolites in dissected tissues were used to localize, quantify, and characterize brain damage after intracerebral injections of Mn2+ into striatum and hippocampus. The specificity of Mn2+-induced lesions is described in relation to brain damage produced by local Fez+ or 6-hydroxydopamine (6-OHDA) injections. In striatum, Fez+ and Mn2+ produced dose-dependent (0.05-0.8 pmol) dopamine (DA) depletion, with Fez+ being 3.4 times more potent than Mn2+. Studies examining the time course of changes in monoamine levels in striatum following local application of 0.4 pmol of Mn2+ revealed maximal depletion of all substances investigated (except 5-hydroxyindoleacetic acid) after 3 days. The effects on DA (87% de-

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