Striatal MPP+Levels do not Necessarily Correlate with Striatal Dopamine Levels after MPTP Treatment in Mice

Abstract

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.