IN-VIVO ELECTROCHEMICAL STUDIES OF DOPAMINE OVERFLOW AND CLEARANCE INTHE STRIATUM OF NORMAL AND MPTP-TREATED RHESUS-MONKEYS

Rapid chronoamperometric recordings, using Nafion-coated carbon-fiber electrodes (30-90 mu m o.d.), were used to investigate overflow and up take of dopamine (DA) in the striatum of normal and 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus monkeys. The monkeys were anesthetized with isoflurane and placed in a stereotaxic apparatu s. Magnetic resonance imaging-guided sterile stereotaxic procedures we re used for implantations of the electrochemical electrodes coupled wi th single-barrel micropipettes that were used to apply potassium or DA locally. Potassium evoked a robust overflow of DA-like electrochemica l signals into the brain extracellular space in the unlesioned or norm al putamen and caudate nucleus of the rhesus monkeys. In contrast, pot assium did not produce any detectable changes (> 97% depletion) of DA in the MPTP-lesioned striatum. In addition, the diffusion/clearance of locally applied DA was markedly altered in the lesioned caudate nucle us and putamen compared with unlesioned striatum. Cell counts of the n umber of residual tyrosine hydroxylase-positive neurons in MPTP-treate d monkeys, in conjunction with whole-tissue levels of DA and its metab olites, showed that the MPTP lesions produced extensive damage of the nigrostriatal DA system. These data indicate that residual dopaminergi c fibers remaining after MPTP lesions are dysfunctional and have a gre atly diminished capacity for high-affinity DA uptake.