Influence of Selective Inhibition of Monoamine Oxidase A or B on Striatal Metabolism of l‐DOPA in Hemiparkinsonian Rats

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Abstract
The effect of selective inhibition of monoamine oxidase (MAO) subtypes A and B on striatal metabolism of DOPA to dopamine (DA), 3,4‐dihydroxyphenylacetic acid (DOPAC), and 4‐hydroxy‐3‐methoxyphenylacetic acid (homovanillic acid; HVA) was studied in halothane‐anesthetized rats 3 weeks 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. The DOPA was administered as a 15‐min bolus of 1 mM solution in the striatal microdialysate. Rats were pretreated with the selective MAO‐A inhibitor clorgyline, or the selective MAO‐B inhibitors deprenyl or TVP‐101 [2,3‐dihydro‐N‐2‐propynyl‐1H‐inden‐1‐amine‐(1R)‐hydrochloride]. Intrastriatal infusion of DOPA caused an increased efflux of DA, DOPAC, and HVA, which 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 inhibitors. There was no evidence for a differential effect of MAO‐B inhibition on efflux of DA or metabolites in the lesioned as compared with the control striatum. The results indicate a major role for MAO‐A in DA metabolism both intra‐ and extraneuronally in the rat striatum.

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