Alteration of striatal [11C]raclopride and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine uptake precedes development of methamphetamine-induced rotation following unilateral 6-hydroxydopamine lesions of medial forebrain bundle in rats.
We studied the positron emission tomography (PET) tracer distributions of ligands for dopamine D1 receptors ([11C]SCH23390) and D2 receptors ([11C]raclopride) and of the dopamine precursor analog 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) in the brain after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The number of methamphetamine-induced rotation was higher at 14 days than at 3 days after the 6-OHDA lesions. The brains of 6-OHDA-treated rats were analyzed by tissue dissection following i.v. bolus of each tracer at 3 days (acute stage) or 3 weeks (chronic stage) postlesion. [11C]Raclopride, but not [11C]SCH23390, showed higher accumulation in the striatum on the lesion side than on the non-lesion (intact) side both at 3 days and 3 weeks postlesion. On the other hand, lower accumulation of [18F]FDOPA was observed in the striatum on the lesion side at 3 days postlesion and in both the striatum and cerebral cortex on the lesion side at 3 weeks postlesion. Our studies demonstrate that an increase in [11C]raclopride and a decrease in [18F]FDOPA uptake in the denervated striatum is evident even at 3 days after the 6-OHDA lesions when the methamphetamine-induced rotational behavior is not established.
Ishida
Yasushi
Y
Department of Psychiatry, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Miyazaki-gun, Miyazaki 889-1692, Japan. ishiday@med.miyazaki-u.ac.jp
Kawai
Keiichi
K
Magata
Yasuhiro
Y
Abe
Hiroshi
H
Yoshimoto
Mitsuyoshi
M
Takeda
Ryuichiro
R
Hashiguchi
Hiroyuki
H
Mukai
Takahiro
T
Saji
Hideo
H
D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D007839:Functional Laterality; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity*; D016548:Prosencephalon / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology; D020891:Raclopride / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D051381:Rats; D012399:Rotation; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D020891:Raclopride; D008694:Methamphetamine; D004295:Dihydroxyphenylalanine; D016627:Oxidopamine