ABSTRACT
The time course of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT) and 3-methoxytyrosine (3-O-Medopa) concentrations in rat brain after treatment with L-dopa + benserazide has been investigated in the striatum, hypothalamus, hippocampus and cerebellum. These areas were selected for their different dopaminergic activities. After L-dopa loading, DA, DOPAC and HVA were increased in all the structures, but the largest increases were in those tissues with the less dopaminergic activity, while 3-MT increased in the hypothalamus, hippocampus and cerebellum but was lowered in striatum. 3-O-Medopa, which is the direct product of the O-methylation of L-dopa, did not show any specific distribution. The data provide evidence that the striatum, by feed-back mechanisms and specific enzymatic activity, is able to ensure a better regulation of dopaminergic activity than the other structures, thereby overcoming excess L-dopa.
Subject(s)
Brain Chemistry/drug effects , Dopamine/metabolism , Levodopa/pharmacology , 3,4-Dihydroxyphenylacetic Acid/metabolism , 5-Methoxytryptamine/metabolism , Animals , Corpus Striatum/metabolism , Hippocampus/metabolism , Homovanillic Acid/metabolism , Male , Rats , Rats, Inbred StrainsABSTRACT
Investigation by HPLC with electrochemical detection of dopamine (DA) metabolism in rat striatum after L-dopa + benserazide treatment allowed quantification of the time course evolution of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Furthermore, four peaks which did not appear in controls, were detected in treated striatum. One was identified as 3-methoxytyrosine, the level of which was still high 9 h after treatment. 3-Methoxytyrosine, has been detected previously in plasma of parkinsonian patients treated with L-dopa, and the disturbance in DA metabolism could explain some of the side-effects induced by that treatment.
