J. Moses et al., SODIUM BENZOATE DIFFERENTIALLY BLOCKS CIRCLING INDUCED BY D-DOPA AND L-DOPA IN THE HEMI-PARKINSONIAN RAT, Neuroscience letters, 218(3), 1996, pp. 145-148
D-3,4-Dihydroxyphenylalanine (D-dopa) and L-3,4-dihydroxyphenylalanine
(L-dopa) induce circling in rats with a unilateral 6-hydroxydopamine
lesion of substantia nigra with similar potency. D-Dopa is not a subst
rate for aromatic L-amino acid decarboxylase, the enzyme which metabol
izes L-dopa to dopamine. This raises the question of how D-dopa has be
havioral effect. Two pathways have been suggested to result in convers
ion of D-dopa to L-dopa, one involving oxidation of D-dopa to dihydrox
yphenylpyruvic acid (DHPPA) by D-amino acid oxidase, the other involvi
ng transamination of D-dopa to DHPPA. Here we show that sodium benzoat
e, an inhibitor of D-amino acid oxidase, blocks D-dopa-induced circlin
g while having no effect on circling induced by L-dopa. The results su
ggest that conversion of D-dopa to L-dopa via DHPPA is highly dependen
t on oxidase activity and that sodium benzoate effectively inhibits th
is process in vivo in rat.