Influence of selective inhibition of monoamine oxidase A or B on striatal metabolism of L-DOPA in hemiparkinsonian rats.
The effect of selective inhibition of monoamine oxidase (MAO) subtypes A and B on striatal metabolism of DOPA to dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid; HVA) was studied in halothane-anesthetized rats 3 weeks after unilateral 6-hydroxydopamine lesion of the substantia nigra. Implantation of bilateral microdialysis probes allowed simultaneous quantitation of metabolite production on lesioned and control sides. The DOPA was administered as a 15-min bolus of 1 mM solution in the striatal microdialysate. Rats were pretreated with the selective MAO-A inhibitor clorgyline, or the selective MAO-B inhibitors deprenyl or TVP-101 [2,3-dihydro-N-2-propynyl-1H-inden-1-amine-(1R)-hydrochloride]. Intrastriatal infusion of DOPA caused an increased efflux of DA, DOPAC, and HVA, which was greater on the intact side. Clorgyline, but not deprenyl or TVP-101, increased post-DOPA DA efflux on both intact and lesioned sides. Clorgyline also caused a marked suppression of post-DOPA DOPAC and HVA effluxes, whereas only mild effects were produced by the MAO-B inhibitors. There was no evidence for a differential effect of MAO-B inhibition on efflux of DA or metabolites in the lesioned as compared with the control striatum. The results indicate a major role for MAO-A in DA metabolism both intra- and extraneuronally in the rat striatum.
Finberg
J P
JP
Clinical Neurosciences Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Wang
J
J
Goldstein
D S
DS
Kopin
I J
IJ
Bankiewicz
K S
KS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007189:Indans / Q000494:pharmacology; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects
D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D007980:Levodopa; D016627:Oxidopamine; D003010:Clorgyline; D004298:Dopamine; D006719:Homovanillic Acid