In vivo PET studies of the dopamine D2 receptors in rhesus monkeys with long-term MPTP-induced parkinsonism.
Studies of dopamine (DA) receptor binding in early parkinsonian patients, or in models of Parkinson's disease, have revealed a supersensitivity of the D2-like receptor subtype as compared to age-matched controls. The lack of upregulation in advanced patients is often attributed to the effects of prolonged antiparkinsonian therapy, but the impact of therapy vs. intrinsic mechanisms in untreated patients or animals with long-term lesions of the DA nigrostriatal pathway has been difficult to address. We studied, in vivo, by PET using the DA D2 receptor ligand raclopride, the status of the DA receptors in normal rhesus monkeys and those with acute (3 months) or long-term (10 years) MPTP-induced nigrostriatal lesions. Compared to age-matched controls, there was no change in raclopride binding in MPTP-treated animals without parkinsonian symptoms. There was a significant increase in raclopride binding in the putamen (but not caudate nucleus) of all the animals displaying rigidity, hypo- and bradykinesia. This increase was greater in the animals with acute lesions (32%) than with established, long-term lesions (18%). There was no correlation between the postmortem striatal DA concentrations and in vivo raclopride binding but there was a correlation between PET raclopride binding and [(3)H]raclopride binding in vitro. Complex changes in D2 receptor binding occur in various stages of parkinsonism. Antiparkinsonian therapy is unlikely to be solely responsible for the lack of upregulation found in advanced parkinsonian patients but may be a contributing factor.
Doudet
D J
DJ
Department of Medicine, Division of Neurology and Kinsmen Laboratory of Neurological Research and TRIUMF, University of British Columbia, Vancouver, BC, Canada. ddoudet@interchange.ubc.ca
Holden
J E
JE
Jivan
S
S
McGeer
E
E
Wyatt
R J
RJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000293:injuries / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents; D005260:Female; D008253:Macaca mulatta; D008297:Male; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D011699:Putamen / Q000293:injuries / Q000378:metabolism*; D020891:Raclopride / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D020891:Raclopride; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine