Biotransformation of L-dopa in striatum and substantia nigra of rats with a unilateral, nigrostriatal lesion: a microdialysis study.
Microdialysis was used to study the biotransformation of L-DOPA in the striatum and substantia nigra of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. The animals were pretreated with carbidopa (50 mg/kg p.o.) for 5 days. They were anaesthetized, and microdialysis probes were implanted into the intact and denervated striatum and into the intact and lesioned substantia nigra. The biotransformation of L-DOPA (5 mg/kg i.p.) in these regions was investigated. These results were compared with those obtained after administration of a much higher dose of L-DOPA (100 mg/kg i.p.). Changes in extracellular L-DOPA, 3-O-methyldopa (3-OMD), dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined by HPLC with electrochemical detection. Although rats with a unilateral nigrostriatal lesion did not show rotational behaviour after 5 mg/kg L-DOPA, DA levels were increased significantly both in the intact and the denervated striatum and in the intact and the lesioned substantia nigra. This increase was most pronounced in the denervated striatum. At 100 mg/kg L-DOPA, the increases in extracellular dopamine in intact and denervated striatum were about twice as high as the increases observed at the lower dose. A similar increase was observed in the intact substantia nigra. However, in the lesioned substantia nigra there was a fourfold increase. L-DOPA, at both doses, was evenly distributed between the brain areas studied and the lesion had no effect on the uptake of the drug at the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
Sarre
S
S
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Belgium.
Herregodts
P
P
Deleu
D
D
Devrieze
A
A
De Klippel
N
N
Ebinger
G
G
Michotte
Y
Y
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D003342:Corpus Striatum / Q000378:metabolism* / Q000502:physiology; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism* / Q000502:physiology
D000777:Anesthetics; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine; D006719:Homovanillic Acid