INFLUENCE OF SELECTIVE-INHIBITION OF MONOAMINE-OXIDASE-A OR MONOAMINE-OXIDASE-B ON STRIATAL METABOLISM OF L-DOPA IN HEMIPARKINSONIAN RATS

The effect of selective inhibition of monoamine oxidase (MAO) subtypes A and B on striatal metabolism of DOPA to dopamine (DA), 3,4-dihydrox yphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid ( homovanillic acid; HVA) was studied in halothane-anesthetized rats 3 w eeks after unilateral 6-hydroxydopamine lesion of the substantia nigra . Implantation of bilateral microdialysis probes allowed simultaneous quantitation of metabolite production on lesioned and control sides. T he DOPA was administered as a 15-min bolus of 1 mM solution in the str iatal microdialysate. Rats were pretreated with the selective MAO-A in hibitor clorgyline, or the selective MAO-B inhibitors deprenyl or TVP- 101 N-2-propynyl-1H-inden-1-amine-(1R)-hydrochloride]. Intrastriatal i nfusion of DOPA caused an increased efflux of DA, DOPAC, and HVA, whic h was greater on the intact side. Clorgyline, but not deprenyl or TVP- 101, increased post-DOPA DA efflux on both intact and lesioned sides. Clorgyline also caused a marked suppression of post-DOPA DOPAC and HVA effluxes, whereas only mild effects were produced by the MAO-B inhibi tors. There was no evidence for a differential effect of MAO-B inhibit ion on efflux of DA or metabolites in the lesioned as compared with th e control striatum. The results indicate a major role for MAO-A in DA metabolism both intra- and extraneuronally in the rat striatum.