Selective decrease in extracellular DOPAC concentrations in rat striatum following in vivo dialysis with low concentrations of MPP+.
Using the technique of in vivo dialysis, 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was applied to the rat striatum and the effects of this treatment on the efflux of striatal dopamine (DA) and metabolites were monitored. The inclusion of low concentrations of MPP+ (1 and 10 microM) in the dialysis solution caused a progressive decrease in the efflux of dihydroxyphenylacetic acid (DOPAC), the major deamination product of DA, while homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) remained unchanged. Unlike the effects of dialysis with millimolar concentrations of MPP+, a large increase in the efflux of striatal DA was not observed. The effect of dialysis with 1 microM MPP+ was blocked if 1 microM GBR 12909, a specific DA reuptake blocker, was included in the dialysis fluid, suggesting uptake of MPP+ into striatal DA terminals mediated this effect.
Caliguri
E J
EJ
National Institute of Mental Health, Laboratory of Clinical Science, Bethesda, MD 20892.
Johannessen
J N
JN
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007700:Kinetics; D051381:Rats
D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D006719:Homovanillic Acid