L-DOPA modulates striatal dopaminergic function in vivo: evidence from PET investigations in nonhuman primates.
Significant increases in striatal L-[11C]DOPA retention were observed in adult female rhesus monkeys with positron emission tomography (PET) following administration of drugs that increase cerebral L-DOPA concentrations. The monkeys were scanned twice: at baseline (using 10-50 micrograms of tracer substance) and during continuous administration of L-DOPA (3 or 15 mg/kg/h) and 6-R-Erythro-4,5,6,7-tetrahydrobiopterin (6R-BH4) (5 mg/kg/h) and during combined administration of both drugs. PET scans of L-[11C]DOPA distribution were obtained in GE2048-15B or GE4096-15WB Plus positron tomographs. In all studies the specific striatal L-[11C]DOPA influx rate increased by an average of 17-20%. These increases were significantly higher than the retest variability obtained with saline infusions under identical experimental conditions. In individual monkeys the magnitude of increase in the striatal L-[11C]DOPA influx rate varied from no effect of the drug infusion to a 45% increase. Taken together, the results of this study demonstrate that L-DOPA in itself can affect dopaminergic neurotransmission in vivo and also adds further evidence that the neuromodulatory effects of the amino acid are predominantly autoreceptor antagonist-like. The findings most likely have importance for the further understanding of the dopaminergic system in neurodegenerative and psychiatric disorders.
Tedroff
J
J
Department of Neurology, University of Uppsala, Sweden.
Torstenson
R
R
Hartvig
P
P
Lindner
K J
KJ
Watanabe
Y
Y
Bjurling
P
P
Westerberg
G
G
Långström
B
B
D000818:Animals; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007980:Levodopa / Q000494:pharmacology*; D008253:Macaca mulatta; D014055:Tomography, Emission-Computed
D007980:Levodopa; D004298:Dopamine