Striatal MPP+ levels do not necessarily correlate with striatal dopamine levels after MPTP treatment in mice.
The present study offers confirmation of the fact that an MAO-B inhibitor, (-) deprenyl and a DA uptake blocker, GBR-12909, prevent MPTP-induced striatal DA decrease. This protective effect is accompanied by an almost complete prevention of MPP+ production induced by (-) deprenyl and an accelerated MPP+ clearance induced by GBR-12909 within the striatum. Similarly, the MPTP toxicity enhancers, DDC and acetaldehyde, both increase striatal MPP+ levels, as previously reported. On the contrary, the treatment with MK 801, although uneffective in preventing the long-term MPTP-induced striatal DA decrease, causes an increase in the striatal amount of MPP+. In a similar way, the administration of nicotine in combination with MPTP produces a significant increase in the levels of striatal MPP+, which does not elicit any effect on striatal DA. The effect of clonidine is consistent with these results and in sharp contrast with the current belief that a direct relationship exists between striatal MPP+ concentrations and the degree of MPTP-induced depletion of striatal DA. In this study, using different treatments, we failed to confirm the correlation between MPP+ striatal levels and dopaminergic lesions after MPTP administration in mice. We suggest that this correlation is not a rule and exceptions may depend on a different compartimentalization of the toxic metabolite.
Vaglini
F
F
Institute of Pharmacology, School of Medicine, University of Pisa, Italy.
Fascetti
F
F
Tedeschi
D
D
Cavalletti
M
M
Fornai
F
F
Corsini
G U
GU
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism* / Q000493:pharmacokinetics; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism* / Q000493:pharmacokinetics; D000079:Acetaldehyde / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004050:Ditiocarb / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D020267:MPTP Poisoning; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D012642:Selegiline; D012701:Serotonin; D016291:Dizocilpine Maleate; D009538:Nicotine; C043425:vanoxerine; D004050:Ditiocarb; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000079:Acetaldehyde; D003000:Clonidine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine