Assessment of dopamine and its metabolites in the intracellular and extracellular compartments of the rat striatum after peripheral administration of l-[ 11C]DOPA

Abstract

Success in the synthesis of l-3,4-[β 11C]dihydroxyphenylalanine ( l[ 11C]DOPA. and its application to positron emission tomography encouraged us to perform radioactive metabolite analyses in rats in an early phase affter peripheral injection of l-[ 11C]DOPA. Following intravenous injection of [ 11C]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 11C-radioactivity taken up into the striatum was associated with acidic metabolites of dopamine (DA) from 2 to 30 min after administration of l-[ 11C]DOPA with or without 300 μg/kg of unlabelled l-DOPA. In contrast, 80–90% of 11C-radioactivity in the striatum was associated with DOPA and DA after pretreatment with benserazide (25 mg/kg, i.p.) followed by administration of l-[ 11C]DOPA with or without unlabelled l-DOPA. The radioactivity in the DOPA fraction decreased with time (from 35% of 11C-radioactivity in the striatum at 5 min to 10% at 30 min), but that in the DA fraction increased (from 57% to 68%). The 11C-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-[ 11C]DOPA, [ 11C]DA is the main metabolite and is localized exclusively in the intracellular compartment within this time frame.