Alteration of striatal [ 11C]raclopride and 6-[ 18F]fluoro- l-3,4-dihydroxyphenylalanine uptake precedes development of methamphetamine-induced rotation following unilateral 6-hydroxydopamine lesions of medial forebrain bundle in rats

Abstract

We studied the positron emission tomography (PET) tracer distributions of ligands for dopamine D 1 receptors ([ 11C]SCH23390) and D 2 receptors ([ 11C]raclopride) and of the dopamine precursor analog 6-[ 18F]fluoro- l-3,4-dihydroxyphenylalanine ([ 18F]FDOPA) in the brain after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The number of methamphetamine-induced rotation was higher at 14 days than at 3 days after the 6-OHDA lesions. The brains of 6-OHDA-treated rats were analyzed by tissue dissection following i.v. bolus of each tracer at 3 days (acute stage) or 3 weeks (chronic stage) postlesion. [ 11C]Raclopride, but not [ 11C]SCH23390, showed higher accumulation in the striatum on the lesion side than on the non-lesion (intact) side both at 3 days and 3 weeks postlesion. On the other hand, lower accumulation of [ 18F]FDOPA was observed in the striatum on the lesion side at 3 days postlesion and in both the striatum and cerebral cortex on the lesion side at 3 weeks postlesion. Our studies demonstrate that an increase in [ 11C]raclopride and a decrease in [ 18F]FDOPA uptake in the denervated striatum is evident even at 3 days after the 6-OHDA lesions when the methamphetamine-induced rotational behavior is not established.