Summary The effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) on the central cholinergic and dopaminergic systems in the Rhesus monkey brain were investigated by positron emission tomography (PET) with the muscarinic cholinergic receptor ligands (N-[
11C]methyl-benztropine) and dopaminergic receptor ligands selective for D
1 D
2, and D
3 subtypes ([
11C]SCH23390, N-[
11C]methyl-spiperone, and (+)[
11C]UH232, respectively). None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP used significantly affected the regional cerebral blood flow (rCBF as determined by Raichle's H
2
15O method), and 10 mg/kg of R-THBP had little effect on the regional cerebral metabolic rate of glucose (rCMRglc) in the Rhesus monkey brain, as assessed by the graphical [
18F]fluoro-deoxyglucose method. The effect of R-THBP on the muscarinic cholinergic system was dose dependent; while 3 mg/kg of R-THBP did not significantly alter the uptake ratio of N-[
11C]methyl-benztropine in several brain regions to that in the cerebellum, 10 and 30 mg/kg of R-THBP significantly reduced the uptake ratio in the thalamus, as well as in the frontal and temporal cortices. None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP tested affected [
11C]SCH23390 (dopamine D
1 receptor) binding. However, the k3 value for N-[
11C]methyl-spiperone (dopamine D
2 receptor) binding, which represents the association rate × B
max value, was significantly decreased in the striatum. The uptake ratio of (+)[
11C]UH232 (dopamine D
3 receptor) in the striatum to that in the cerebellum was also decreased by administration of R-THBP (3 and 30 mg/kg i.v.). These findings suggest that R-THBP acts on dopamine D
2 and D
3 receptors selectively without markedly affecting dopamine D
1 receptor binding. Furthermore, the changes in cholinergic and dopamine D
2 and D
3 receptors in vivo can not be attributed to a change in rCBF but may depend on the action of R-THBP.Abbreviations
R-THBP
6R-L-erythro-5,6,7,8-tetrahydrobiopterin
-
PET
positron emission tomography
-
rCBF
regional cerebral blood flow
-
rCMRglc
regional cerebral metabolic rate of glucose
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