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Suppression of L-dopa-induced circling in rats with nigral lesions by blockade of central dopa-decarboxylase: implications for mechanism of action of L-dopa in parkinsonism.

Abstract
Dopamine (DA) elevations in rat striatum produced by combined administration of L-dopa and carbidopa were abolished when L-dopa was injected with NSD-1015, an inhibitor of central dopa-decarboxylase. In all rats with unilateral 6-OH-DA nigral lesions, L-dopa-induced contraversive circling occurred after carbidopa, but was totally abolished (in 60%) or markedly suppressed after pretreatment with NSD-1015. Administration of the DA metabolites DOPAC and HVA systemically and of 3-methoxytyramine intrastriatally evoked no circling in animals with 6-OH-DA lesions. In rats with unilateral nigrotomies, the direction of L-dopa-induced circling was reversed and became ipsiversive after DA receptors were reduced by the addition of kainic acid lesions in ipsilateral striata. Findings provide evidence that circling in rats--and by analogy, efficacy in parkinsonians--requires the decarboxylation of exogenous L-dopa and interaction of the formed DA with DA receptors in striatum.
AuthorsE Melamed, F Hefti, V Bitton, M Globus
JournalNeurology (Neurology) Vol. 34 Issue 12 Pg. 1566-70 (Dec 1984) ISSN: 0028-3878 [Print] United States
PMID6504328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Dopamine Antagonists
  • Hydrazines
  • Receptors, Dopamine
  • Levodopa
  • 3-hydroxybenzylhydrazine
  • Dopa Decarboxylase
  • Dopamine
Topics
  • Animals
  • Behavior, Animal (drug effects)
  • Corpus Striatum (drug effects, metabolism)
  • Dopa Decarboxylase (pharmacology)
  • Dopamine (metabolism)
  • Dopamine Antagonists
  • Hydrazines (metabolism, pharmacology)
  • Levodopa (metabolism, pharmacology)
  • Male
  • Parkinson Disease (drug therapy, metabolism)
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine (metabolism)
  • Substantia Nigra (drug effects, metabolism)

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