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L-DOPA modulates striatal dopaminergic function in vivo: Evidence from PET investigations in nonhuman primates

✍ Scribed by J. Tedroff; R. Torstenson; P. Hartvig; K.J. Lindner; Y. Watanabe; P. Bjurling; G. Westerberg; B. Langström


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
66 KB
Volume
25
Category
Article
ISSN
0887-4476

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✦ Synopsis


Significant increases in striatal L-[ 11 C]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 µg of tracer substance) and during continuous administration of L-DOPA (3 or 15 mg/kg/h) and 6-R-Erythro-4,5,6,7tetrahydrobiopterin (6R-BH 4 ) (5 mg/kg/h) and during combined administration of both drugs. PET scans of L-[ 11 C]DOPA distribution were obtained in GE2048-15B or GE4096-15WB Plus positron tomographs. In all studies the specific striatal L-[ 11 C]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-[ 11 C]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.