Document Detail


Opioid antagonists increase the dyskinetic response to dopaminergic agents in parkinsonian monkeys: interaction between dopamine and opioid systems.
MedLine Citation:
PMID:  14573388     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pathogenesis of levodopa-induced dyskinesias (LID) still remains obscure. It has been suggested that enhanced opioidergic transmission in striatal output pathways may play a role in the induction of LID. To test this hypothesis, we have investigated the effect of different doses of the opioid receptor antagonists, naloxone and naltrexone on the dyskinetic response to a D1 agonist SKF 82958, a D2 agonist quinpirole and L-3,4-dihydroxyphenylalanine (L-Dopa). We have used six female cynomolgus monkeys rendered parkinsonian by the toxin MPTP and presenting a stable parkinsonian syndrome. All responded to L-Dopa and had developed dyskinesias which were manifested with each dose. The parkinsonian syndrome and dyskinesias were evaluated for each animal and scored after the treatments. Locomotor activity was measured by an electronic motility monitoring system. Our results show that coadministration of naloxone or naltrexone with dopaminergic agents leads to a significant increase in the severity of dyskinesias without noticeable effect on the antiparkinsonian efficacy of the treatment. These results suggest that increased opioidergic transmission in the two major striatal output pathways in monkeys or humans with LID might be an attempt to dampen the effect of abnormal dopaminergic stimulation rather than the cause of dyskinesias.
Authors:
Pershia Samadi; Laurent Grégoire; Paul J Bédard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuropharmacology     Volume:  45     ISSN:  0028-3908     ISO Abbreviation:  Neuropharmacology     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-10-23     Completed Date:  2003-12-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  954-63     Citation Subset:  IM    
Affiliation:
Unité de recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, 2705 Boulevard Laurier, Sainte-Foy, Quebec G1V 4G2, Canada.
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Benzazepines / pharmacology
Dopamine / physiology*
Dopamine Agents / toxicity*
Dopamine Agonists / pharmacology
Dyskinesia, Drug-Induced / physiopathology*
Endorphins / physiology*
Female
Levodopa / pharmacology
Macaca fascicularis
Motor Activity / drug effects
Naloxone / pharmacology
Naltrexone / pharmacology
Narcotic Antagonists / pharmacology*
Parkinson Disease, Secondary / chemically induced,  physiopathology*
Quinpirole / pharmacology
Receptors, Dopamine D1 / agonists
Receptors, Dopamine D2 / agonists
Synaptic Transmission / drug effects
Chemical
Reg. No./Substance:
0/Benzazepines; 0/Dopamine Agents; 0/Dopamine Agonists; 0/Endorphins; 0/Levodopa; 0/Narcotic Antagonists; 0/Receptors, Dopamine D1; 0/Receptors, Dopamine D2; 16590-41-3/Naltrexone; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 465-65-6/Naloxone; 80751-65-1/SK&F 82958; 85760-74-3/Quinpirole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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