Imaging of Pre- and Post-synaptic Adaptations in the Nigrostriatal Dopaminergic System of MPTP-induced Parkinsonism

A selective destruction of the nigrostriatal dopaminergic neurons by a systemic administration of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP, 1.5 to 2.5 mg/kg, i.v.) to rhesus monkeys causes a persistent parkinsonian syndrome (Burns et al., 1983). A near complete depletion of the striatal dopamine (DA) content induces an increase in the ratio of homovanillic acid to DA, a sprouting of the survived DA neurons, an up-regulation of tyrosine hydroxylase and L-aromatic amino acid decarboxylase and a supersensitivity in motor response to DA agonists (Chiueh, 1987). We used this primate model of parkinsonism in developing and evaluation of pre- and post-synaptic imaging ligands of DA neurons for in vivo brain imaging procedures, i.e., positron emission tomography (PET) and single photon emission computerized tomography (SPECT) and ex vivo autoradiography. In the present study, the MPTP-induced destruction of the DA nerve terminals in the basal ganglia was visualized in vivo by using a pre-synaptic PET ligand, 6-[F-18]-DOPA synthesized by Firnau et al. (1984). The denervation-induced supersensitive D-2 DA receptors in the caudate nucleus and putamen were imaging by a newly developed post-synaptic SPECT ligand, 3-[I-123]-IBZM (Kung et al., 1987) in unilaterally-lesioned animals.