Changes in dopamine D2 receptors and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine uptake in the brain of 6-hydroxydopamine-lesioned rats.
We studied tracer distributions in positron emission tomography of ligands for dopamine D1 receptors ([11C]SCH23390) and D2 receptors ([11C]raclopride) and the dopamine precursor analog 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA), as a measurement of presynaptic dopaminergic function, in the brain after 6-hydroxydopamine lesioning of the medial forebrain bundle in rats. The unilateral lesions were confirmed behaviorally by methamphetamine-induced rotation 2 weeks after lesioning, and the brains were analyzed by tissue dissection following an intravenous bolus of each tracer 3 weeks after lesioning. [11C]Raclopride, but not [11C]SCH23390, showed a higher accumulation in the striatum on the lesion side compared with that on the non-lesioned (intact) side. On the other hand, a lower accumulation of [18F]FDOPA was found in the striatum and cerebral cortex on the lesion side. Our studies demonstrate upregulation of dopamine D2 receptors in the striatum and a decrease in FDOPA uptake in both the striatum and cerebral cortex ipsilateral to the 6-hydroxydopamine lesions. Therefore, the combination of a D2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease.
Ishida
Yasushi
Y
Department of Psychiatry, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan. ishiday@med.miyazaki-u.ac.jp
Kawai
Keiichi
K
Magata
Yasuhiro
Y
Takeda
Ryuichiro
R
Hashiguchi
Hiroyuki
H
Abe
Hiroshi
H
Mukai
Takahiro
T
Saji
Hideo
H
D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism; D008024:Ligands; D008297:Male; D017072:Neostriatum / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D020891:Raclopride / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013563:Sympathectomy, Chemical; D013565:Sympatholytics / Q000633:toxicity*; D014018:Tissue Distribution
D001552:Benzazepines; D018492:Dopamine Antagonists; D008024:Ligands; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; C043437:fluorodopa F 18; D020891:Raclopride; D004295:Dihydroxyphenylalanine; D016627:Oxidopamine