CHRONIC EFFECTS OF SINGLE INTRASTRIATAL INJECTIONS OF 6-HYDROXYDOPAMINE OR 1-METHYL-4-PHENYLPYRIDINIUM STUDIED BY MICRODIALYSIS IN FREELY MOVING RATS

Extracellullar dopamine (DA) and its main cerebral metabolites, dihydr oxyphenylacetic acid (DOPAC) and homovanillic acid (KVA), were measure d by bilateral striatal microdialysis in rats at different times (2, 7 , 15 and 60 days) after unilateral administration into the right stria tum of 1-methyl-4-phenylpyridinium ion (MPP(+)) or 6-hydroxydopamine ( 6-OHDA). In both cases the decrease in extracellullar dopamine did not exceed 40% of control values. The response of DOPAC and HVA depended on the treatment: MPP(+) caused a marked acute decrease in the dopamin e metabolites but allowed a progressive recovery that was very evident after 60 days; 6-OHDA caused a progressive decrease in the dopamine m etabolites throughout the two months of the study. Tyrosine hydroxylas e immunostaining revealed severe neuronal loss in substantia nigra two months after striatal administration of 6-OHDA, whereas no significan t neuronal loss was found at the same time after MPP(+) administration . A bilateral challenge infusion of MPP(+) through the microdialysis p robe was used to assess the dopaminergic capacity of both striata: at all the times studied there was a sharp depletion of DA on the non-les ioned side; both MPP(+)- and 6-OHDA-treated striata were unresponsive after a short time (2 days); after 2 months the response in MPP(+)-les ioned rats was similar on both sides, whereas 6-OHDA-lesioned striata were still unresponsive to MPP(+). In rats, then, the effects of MPP() could be partly reversed whereas the effects of 6-OHDA were not. The se results suggest that neurotoxins causing striatal dopamine loss may act through different mechanisms, which could be significant for the etiopathogenic development of Parkinson's disease.