[Effect of L-DOPA on brain serotonin metabolism related to tryptophan concentrations in plasma and brain of rats]

Abstract

Changes in tryptophan (Trp) concentrations in the peripheral and brain tissues and their influences on brain serotonin (5-HT) metabolism were investigated after i.p. administrations of L-DOPA alone and in combination with Ro4-4602 in male Wistar rats. L-DOPA alone elicited marked increases of both plasma free and liver Trp levels, and a slight increase of brain Trp level. Concomitant application of L-DOPA and Ro4-4602 did not change peripheral Trp concentrations but did reduce brain Trp level. Brain 5-HT levels were reduced in proportion to the increase of dopamine (DA) level by L-DOPA alone and Ro4-4602 plus L-DOPA. A marked increase of 5-HIAA level was exhibited by L-DOPA alone, while Ro4-4602 plus L-DOPA increased 5-HIAA levels slightly despite a marked decrease in 5-HT levels. The decrease of 5-HT and increase of 5-HIAA levels were also observed after administration of L-DOPA to neonatal rats in which the brain tryptophan hydroxylase was considered to be saturated. These results suggest that changes in 5-HT metabolism after L-DOPA injections are not only caused by DA which displaces 5-HT from vesicular stores, but also by changes in Trp concentrations in the plasma and brain which alter 5-HT synthesis and turnover.