Sodium benzoate differentially blocks circling induced by D-and L-dopa in the hemi-parkinsonian rat

D-3,4-Dihydroxyphenylalanine (D-dopa) and L-3,4-dihydroxyphenylalanine (L-dopa) induced circling in rats with a unilateral 6-hydroxydopamine lesion of substantia nigra with similar potency. D-Dopa is not a substrate for aromatic L-amino acid decarboxylase, the enzyme which metabolizes L-dopa to dopamine. This raises the question of how D-dopa has behavioral effect. Two pathways have been suggested to result in conversion of D-dopa to L-dopa, one involving oxidation of D-dopa to dihydroxyphenylpyruvic acid (DHPPA) by D-amino acid oxidase, the other involving transamination of D-dopa to DHPPA. Here we show that sodium benzoate, an inhibitor of D-amino acid oxidase, blocks D-dopa-induced circling while having no effect on circling induced by L-dopa. The results suggest that conversion of D-dopa to L-dopa via DHPPA is highly dependent on oxidase activity and that sodium benzoate effectively inhibits this process in vivo in rat.