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.