Biotransformation of locally applied L-dopa in the corpus striatum of the hemi-parkinsonian rat studied with microdialysis.

Microdialysis was used to study the biotransformation of L-dopa in intact and denervated striata of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. Microdialysis probes were placed in the intact and in the denervated striatum. Observations were then made on freely moving rats. Extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid; HVA) were monitored before, during and after the local administration of L-dopa via the microdialysis probe for 20 min. A dose-dependent increase in extracellular dopamine levels was seen in intact striatum after application of L-dopa in concentrations ranging between 100 nmol/l and 10 mumol/l. In the denervated striatum, the severity of the lesion influenced dopamine formation, so that no dose-effect relation could be established. The effects of the continuous intra striatal infusion of nomifensine, tetrodotoxin or benserazide on the L-dopa-induced dopamine outflow revealed that in the intact striatum this dopamine release is mainly voltage dependent. It was concluded that in the denervated striatum other cells of non-neuronal origin and containing aromatic L-amino acid decarboxylase make a major contribution to the increase in extracellular dopamine levels. Furthermore, L-dopa itself shows no dopamine-releasing properties, at least under the present experimental conditions.