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Selective decrease in extracellular DOPAC concentrations in rat striatum following in vivo dialysis with low
E J Caliguri1, J N Johannessen
1National Institute of Mental Health, Laboratory of Clinical Science, Bethesda, MD 20892.
Brain Research
|May 10, 1991
Summary
Low concentrations of 1-methyl-4-phenylpyridinium (MPP+) reduced dopamine metabolite efflux in rat striatum. This effect was blocked by a dopamine reuptake inhibitor, suggesting MPP+ uptake into dopamine terminals mediates its impact.
Area of Science:
- Neuroscience
- Neuropharmacology
- Toxicology
Background:
- 1-methyl-4-phenylpyridinium (MPP+) is the neurotoxic metabolite of MPTP.
- MPTP is implicated in Parkinsonism.
- Understanding MPP+ neurotoxicity mechanisms is crucial.
Purpose of the Study:
- To investigate the effects of low MPP+ concentrations on dopamine (DA) and its metabolites in the rat striatum.
- To elucidate the mechanism of MPP+ action on striatal neurotransmitter efflux.
Main Methods:
- In vivo dialysis technique was used to perfuse the rat striatum with MPP+.
- Efflux of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) was monitored.
- The effect of a dopamine reuptake blocker (GBR 12909) on MPP+ action was assessed.
Main Results:
- Low MPP+ concentrations (1 and 10 microM) progressively decreased DOPAC efflux.
- Homovanillic acid and 5-hydroxyindoleacetic acid efflux remained unchanged.
- A significant increase in striatal DA efflux was not observed with low MPP+ concentrations.
- The reduction in DOPAC efflux by 1 microM MPP+ was blocked by GBR 12909.
Conclusions:
- MPP+ uptake into striatal dopamine terminals, mediated by the dopamine transporter, appears to be responsible for its effects on dopamine metabolism.
- This suggests a specific mechanism of neurotoxicity distinct from high-concentration effects.
- Findings contribute to understanding the neurotoxic pathways relevant to MPTP-induced neurodegeneration.