Effect of L-dopa loading on 5-HTP decarboxylation in rat brain areas.
The time course of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in four rat brain areas (hypothalamus, hippocampus, striatum and olfactory bulbs) were investigated after treatment with L-dopa (125 mg/kg, ip) + benserazide (50 mg/kg, ip). 5-HTP levels increased as early as 0.5 h, showed maximum accumulation at 1.5 h and returned to control levels within 4 h, while 5-HT was markedly decreased in all four structures, with a maximum effect at 1.5 h (approximately -70%) in the four areas. The decrease in 5-HT was not accompanied by changes in 5-HIAA levels. In agreement with previous studies, these data demonstrate that L-dopa loading interferes with serotonin metabolism in the rat brain. However, in addition to the releasing action of newly-synthesized dopamine, the accumulation of 5-HTP and the parallel decrease in 5-HT indicate a reduction in 5-HT synthesis. This inhibition could be explained by a competitive effect of L-dopa for aromatic aminoacid decarboxylase activity.
Trouvin
J H
JH
UA CNRS 594, Faculté de Pharmacie, Châtenay-Malabry, France.
Maubrey
M C
MC
Raynal
H
H
Jacquot
C
C
D006916:5-Hydroxytryptophan / Q000378:metabolism*; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D003653:Decarboxylation; D006624:Hippocampus / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009830:Olfactory Bulb / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D001545:Benserazide; D006916:5-Hydroxytryptophan