L-DOPA MODULATES STRIATAL DOPAMINERGIC FUNCTION IN-VIVO - EVIDENCE FROM PET INVESTIGATIONS IN NONHUMAN-PRIMATES

Significant increases in striatal L-[C-11]DOPA retention were observed in adult female rhesus monkeys with positron emission tomography (PET ) following administration of drugs that increase cerebral L-DOPA conc entrations. The monkeys were scanned twice: at baseline (using 10-50 m u g of tracer substance) and during continuous administration of L-DOP A (3 or 15 mg/kg/h) and 6-R-Erythro-4,5,6,7-tetrahydrobiopterin (6R-BH 4) (5 mg/kg/h) and during combined administration of both drugs. PET s cans of L-[C-11]DOPA distribution were obtained in GE2048-15B or GE409 6-15WB Plus positron tomographs. In all studies the specific striatal L-[C-11]DOPA influx rate increased by an average of 17-20%. These incr eases were significantly higher than the retest variability obtained w ith saline infusions under identical experimental conditions. In indiv idual monkeys the magnitude of increase in the striatal L-[C-11]DOPA i nflux rate varied from no effect of the drug infusion to a 45% increas e. Taken together, the results of this study demonstrate that L-DOPA i n itself can affect dopaminergic neurotransmission in vivo and also ad ds further evidence that the neuromodulatory effects of the amino acid are predominantly autoreceptor antagonist-like, The findings most lik ely have importance for the further understanding of the dopaminergic system in neurodegenerative and psychiatric disorders. (C) 1997 Wiley- Liss, Inc.