ASSESSMENT OF DOPAMINE AND ITS METABOLITES IN THE INTRACELLULAR AND EXTRACELLULAR COMPARTMENTS OF THE RAT STRIATUM AFTER PERIPHERAL ADMINISTRATION OF L-[C-11]DOPA

Success in the synthesis Of L-3,4-[beta-C-11]dihydroxyphenylalanine (L-[C-11]DOPA) and its application to positron emission tomography encouraged us to perform radioactive metabolite analyses in rats in an early phase after peripheral injection Of L-[C-11]DOPA. Following intravenous injection of [C-11]DOPA, the radioactivity associated with DOPA and its metabolites was determined in the striatum after decapitation and in striatal extracellular fluid using in vivo brain microdialysis. Without pretreatment, 70-80% of C-11-radioactivity taken up into the striatum was associated with acidic metabolites of dopamine (DA) from 2 to 30 min after administration Of L[C-11]DOPA with or without 300-mu-g/kg of unlabelled L-DOPA. In contrast, 80-90% of C-11-radioactivity in the striatum was associated with DOPA and DA after pretreatment treatment with benserazide (25 mg/kg, i.p.) followed by administration Of L-[C-11]DOPA with or without unlabelled L-DOPA. The radioactivity in the DOPA fraction decreased with time (from 35% of C-11-radioactivity in the striatum at 5 min to 10% at 30 min), but that in the DA fraction increased (from 57% to 68%). The C-11-radioactivity in the extracellular fluid determined by brain microdialysis was less than 0.4% of that in the whole striatum and no radioactivity was present in the DA fraction. These results suggest that, in an early phase after administration of L-[C-11]DOPA, [C-11]DA is the main metabolite and is localized exclusively in the intracellular compartment within this time frame.