Effects of different monoamine oxidase inhibitors on the metabolism of L-dopa in the rat brain

Abstract

The influence of monoamine oxidases A and B on the metabolism of dopamine or the expanded dopamine pool following L-dopa administration remains unclear. This study found that treatment of Sprague-Dawley rats with monoamine oxidase inhibitors strongly affected L-dopa metabolism in the brain, but the influence varied with each individual inhibitor. In animals pretreated with pargyline or clorgyline, L-dopa administration led to huge accumulations of dopamine and significantly raised central norepinephrine concentrations. In contrast, similar L-dopa injections in deprenyl-pretreated rats caused only a moderate rise in dopamine and no change in norepinephrine. There seems to be little relationship between the degree of monoamine oxidase inhibition and the accumulation of catecholamines and their metabolites in the rat brain. The effects of monoamine oxidase inhibitors on dopamine accumulation appeared to occur outside the catecholaminergic neurons since in the animals pretreated with 6-hydroxydopamine, which decreased significantly the content of brain catecholamines, dopamine accumulation following L-dopa administration still remained considerable. On the other hand, the influence of monoamine oxidase inhibitors on brain norepinephrine concentrations seemed to originate in the noradrenergic neurons because norepinephrine increase was greatly reduced in rats treated with 6-hydroxydopamine but was restored when the treatment with 6-hydroxydopamine was accompanied by desimipramine which specifically protects noradrenergic stores.