DOPAMINE TERMINAL LOSS AND ONSET OF MOTOR SYMPTOMS IN MPTP-TREATED MONKEYS - A POSITRON EMISSION TOMOGRAPHY STUDY WITH C-11 CFT

We studied the time course of dopamine (DA) terminal loss in three macaca fascicularis injected with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intravenously every 10-14 days for up to 389 days. Striatal DA terminal loss was monitored in vivo by positron emission tomography using C-11-CFT (WIN 35,428), a cocaine derivative that labels the DA transporter. The C-11-CFT uptake rate constant in the striatum of MPTP-treated monkeys decreased exponentially over time, with the putamen significantly more affected than the caudate. Spontaneous locomotor activity decreased in parallel with the decline of the C-11-CFT uptake rate; however, overt parkinsonian signs appeared only after the C-11-CFT uptake rate had declined to about 30% of the pretreatment values. We conclude that a long-term intermittent mode of administration of MPTP can lead to a pattern of terminal loss that closely resembles idiopathic Parkinson disease. (C) 1994 Academic Press, Inc.