Dopamine terminal loss and onset of motor symptoms in MPTP-treated monkeys: a positron emission tomography study with 11C-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 11C-CFT (WIN 35,428), a cocaine derivative that labels the DA transporter. The 11C-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 11C-CFT uptake rate; however, overt parkinsonian signs appeared only after the 11C-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.
Wüllner
U
U
Neuroregeneration Laboratories, McLean Hospital, Belmont, Massachusetts.
Pakzaban
P
P
Brownell
A L
AL
Hantraye
P
P
Burns
L
L
Shoup
T
T
Elmaleh
D
D
Petto
A J
AJ
Spealman
R D
RD
Brownell
G L
GL
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D009043:Motor Activity; D009411:Nerve Endings / Q000000981:diagnostic imaging / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D011699:Putamen / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D014055:Tomography, Emission-Computed / Q000379:methods
D002250:Carbon Radioisotopes; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003042:Cocaine; D004298:Dopamine