Changes in uric acid during acute infusion of MPP(+), 6-OHDA, and FeCl3 - A microdialysis study in the substantia nigra of the guinea pig

Extracellular uric acid levels were measured in the substantia nigra of guinea pigs via microdialysis/liquid chromatography with electrochemical detection (LCED) during infusion (60 min) of N-methyl-4-phenylpyridinium (MPP(+)), 6-hydroxydopamine (6-OHDA), or iron (III) chloride (FeCl3). Striatal and substantia nigra (SN) tissues were analyzed for uric acid (UA) and dopamine (DA) 3 h postinfusion. MPP(+) infusion resulted in an increase in extracellular UA of 222 +/- 6%. The ipsilateral/contralateral ratio of nigral UA tissue levels was significantly increased over vehicle controls. Infusion of 6-OHDA produced an increase of 362 +/- 44% in extracellular UA. No significant changes were seen in UA tissue levels in either the striatum or the SN. Infusion of FeCl3 produced a significant decrease in extracellular nigral UA levels to 21.5 +/- 0.7% of preinfusion levels. The ipsilateral/ contralateral ratio of nigral UA tissue levels increased by 38%, whereas the striatal ratio value decreased to 62% of the vehicle control levels. No changes in DA tissue levels were observed in any of the brain regions in the experimental groups. These results indicate that infusion of neurotoxins known to affect dopaminergic cells generates an acute change in UA levels within the nigrostriatal system of guinea pigs.