Unilateral MPTP lesion in a rhesus monkey: effects on the striatal dopaminergic system measured in vivo with PET using various novel tracers.
We have produced in one monkey a unilateral lesion of the dopaminergic nigrostriatal pathway by slowly infusing 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) into the right internal carotid artery, resulting in contralateral hemiparkinsonism. This procedure was combined with a series of positron emission tomography scans before and after the lesion, using several dopaminergic tracers in parallel. We show that specific binding of [11C]nomifensine in the lesioned striatum disappears to a large extent (80-90%) as a result of the lesion, indicating a corresponding loss of striatal dopamine re-uptake binding sites and thus of the dopamine nerve terminal pool. The uptake of radioactivity in the striatum contralateral to the lesion remained unchanged. In parallel, an early increase in ipsilateral [11C]raclopride binding, indicating upregulation of dopamine D2 receptors, was seen following the presynaptic lesion. [11C]Deprenyl uptake, indicating monoamine oxidase type B enzyme concentration, did not change after the lesion.
Leenders
K L
KL
MRC Cyclotron Unit, Hammersmith Hospital, London, U.K.
Aquilonius
S M
SM
Bergström
K
K
Bjurling
P
P
Crossman
A R
AR
Eckernas
S A
SA
Gee
A G
AG
Hartvig
P
P
Lundqvist
H
H
Långström
B
B
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008253:Macaca mulatta; D009627:Nomifensine / Q000378:metabolism; D011725:Pyridines / Q000633:toxicity*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011725:Pyridines; D011954:Receptors, Dopamine; D009627:Nomifensine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine