Estimation of D2-like receptor occupancy by dopamine in the putamen of hemiparkinsonian Monkeys.
To advance understanding of the neurochemical changes in Parkinson's disease (PD), we compared D2-like dopamine receptor occupancy by dopamine in the control and lesioned putamen of four pig-tailed macaques treated unilaterally with MPTP. PET and in vitro binding techniques were used to measure binding potential (BP(*)) and density of D2-like dopamine receptors (B(max)), respectively. As would be expected in PD, relatively higher values of BP(*) and B(max) and less amphetamine-induced decrease in [(11)C]raclopride binding were observed in the lesioned compared with the contralateral putamen in each animal. The percent differences between lesioned and contralateral sides were similar whether the measurements were of [(11)C]raclopride BP(*) or B(max) values, measured in vivo and in vitro, respectively. As [(11)C]raclopride BP(*) is a measure of the density of D2-like dopamine receptors available for radioligand binding (i.e., not occupied by dopamine), these findings suggest that the fractional occupancy of receptors by endogenous dopamine in the lesioned putamen is nearly equal to that in the contralateral putamen. Therefore, the absolute number of receptors occupied by dopamine, which is a product of receptor density and fractional occupancy by dopamine, is greater in the lesioned than in the contralateral putamen. One possible explanation for the lack of differences in fractional occupancy of D2 receptors by dopamine (despite a loss in available dopamine) is a lesion-induced increase in a portion of low-affinity D2 receptors to a state of high affinity for dopamine.
Chefer
Svetlana I
SI
Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, Baltimore, MD, USA.
Kimes
Alane S
AS
Matochik
John A
JA
Horti
Andrew G
AG
Kurian
Varughese
V
Shumway
Dean
D
Domino
Edward F
EF
London
Edythe D
ED
Mukhin
Alexey G
AG
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D007700:Kinetics; D008254:Macaca nemestrina; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
D017448:Receptors, Dopamine D2; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine