DIFFERENTIAL TIME COURSES OF EXOGENOUS 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AND ITS METABOLITE MPP-ACCUMBENS MEASURED USING IN-VIVOVOLTAMMETRY( IN THE RAT STRIATUM AND NUCLEUS)

The dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridi ne (MPTP) has been shown to affect nigrostriatal projection neurons to a greater extent than substantia nigra neurons that project to the nu cleus accumbens. To investigate this preferential vulnerability, the i ntracerebral pharmacokinetics of locally-applied MPTP was investigated using in vivo voltammetry. First, we examined whether MPTP and MPP+ w ere measurable in vitro. At the most efficient oxidation potential for MPTP (850 mV), its metabolite MPP+ was also partly oxidized, whereas at that for MPP+ (650 mV), MPTP was not oxidized. Then, in vivo measur ements were taken less than 1 mm from the site of infusion of MPTP. MP TP and endogenously produced MPP+ peaked later and took longer to retu rn to baseline in the nucleus accumbens than in the striatum. Systemic monoamine oxidase-B inhibitor pargyline delayed the peak and return t o baseline of endogenously produced MPP+ in the nucleus accumbens. Exo genously applied MPP+ also took longer to peak and return to baseline in the nucleus accumbens. These results indicate that the difference i n the pharmacokinetics of exogenously applied MPTP in the striatum and nucleus accumbens may be due to a difference in uptake in these regio ns, and that the difference in pharmacokinetics of endogenously produc ed MPP+ may be due to differences in both uptake and monoamine oxidase -B activity. (C) 1998 Elsevier Science B.V. All rights reserved.