Pergolide potentiates L-DOPA-induced dopamine release in rat striatum after lesioning with 6-hydroxydopamine.
We used intrastriatal microdialysis to study the effect of pergolide, a D1/D2 dopamine (DA) receptor agonist on biotransformation of exogenous L-DOPA in hemi-Parkinsonian rats. DA and metabolites were assayed by microbore liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 67% and 87% decrease in striatal EC levels of DA in intact and denervated striatum respectively. In intact striatum but not in denervated striatum, pergolide decreased EC levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) (53% and 42% decrease, respectively). L-DOPA (100 mg/kg, i.p.) produced significant increase in EC levels of DA, DOPAC and HVA in intact and denervated striatum with and without local perfusion of 10(-4) M pergolide. In denervated striatum, L-DOPA-induced DA increase was significantly higher in rats with pergolide. Our results suggest that, in an animal model of Parkinson's disease, pergolide in association with L-DOPA favors the restoration of striatal EC DA levels.
Dethy
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Service de Neurologie, ULB-Hôpital Erasme, Brussels, Belgium.
Laute
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MA
Damhaut
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Goldman
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004357:Drug Synergism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism; D010479:Pergolide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018491:Dopamine Agonists; D015102:3,4-Dihydroxyphenylacetic Acid; D010479:Pergolide; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine; D000661:Amphetamine; D004298:Dopamine; D006719:Homovanillic Acid