D-DOPA and l-DOPA similarly elevate brain dopamine and produce turning behavior in rats

Abstract

In the intact rat, intragastric administration of d-dihydroxyphenylalanine ( d-DOPA) together with carbidopa (alpha-methyldopahydrazine, a peripheral dopadecarboxylase inhibitor) increased striatal dopamine concentration to the same extent as a similar treatment with l-DOPA plus carbidopa. In rats with unilateral 6-hydroxydopamine-induced lesions of their substantia nigra, both stereoisomers of DOPA produced significant increases in dopamine and its metabolites in the intact striata. Although dopamine concentrations in the lesioned striata did not change, a significant increase in dopamine metabolites was observed, indicating some extraneuronal formation of dopamine. These results suggest that d-DOPA can be converted to dopamine in the normal striatum as well as in the striatum devoid of dopamine nerve terminals. d- and l-DOPA produced turning behavior in unilaterally lesioned rats with a similar efficacy. The onset of turning after d-DOPA was delayed compared with l-DOPA. Turning behavior elicited by these amino acids was attributed to stimulation of supersensitive dopamine receptors in the lesioned striata by the extraneuronally formed dopamine. Preliminary results suggest that d-DOPA is converted to dopamine via transamination and/or d-amino acid oxidation to 3,4-dihydroxyphenylpyruvic acid which upon further transamination gives rise to l-DOPA and hence dopamine. The relatively fast and slow onset of stimulation of dopamine receptors by l-DOPA and d-DOPA respectively suggests that the use of the racemic mixture of DOPA combined with a peripheral dopadecarboxylase inhibitor may prove useful in the treatment of parkinsonism.