Nicotine reduces levodopa‐induced dyskinesias in lesioned monkeys
Identifieur interne : 001002 ( Main/Exploration ); précédent : 001001; suivant : 001003Nicotine reduces levodopa‐induced dyskinesias in lesioned monkeys
Auteurs : Maryka Quik [États-Unis] ; Heather Cox [États-Unis] ; Neeraja Parameswaran [États-Unis] ; Kathryn O'Leary [États-Unis] ; J. William Langston [États-Unis] ; Donato Di Monte [États-Unis]Source :
- Annals of Neurology [ 0364-5134 ] ; 2007-12.
Abstract
Objective: Levodopa, the gold standard for Parkinson's disease treatment, is associated with debilitating abnormal involuntary movements or dyskinesias, for which few treatments are currently available. Studies have implicated numerous neurotransmitters in the development of levodopa‐induced dyskinesias. However, the cholinergic system has received little attention despite an extensive overlap between dopaminergic terminals and cholinergic interneurons in the striatum and the well‐known ability of nicotine to stimulate striatal dopamine release. Our objective, therefore, was to determine whether nicotine treatment reduced levodopa‐induced dyskinesias. Methods: The effect of nicotine (provided in the drinking water) was determined on dyskinesias induced by levodopa (5mg/kg twice daily by oral gavage) in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)–treated monkeys. Results: Nicotine pretreatment reduced peak and total levodopa‐induced dyskinesias in levodopa‐naive monkeys over an 8‐week period, with a decrease in total dyskinesias of about 50%. A crossover study was then done in which levodopa‐treated monkeys originally receiving vehicle were administered nicotine, whereas the levodopa‐treated animals initially receiving nicotine were placed on vehicle. Nicotine treatment to levodopa‐primed monkeys led to an approximately 35% reduction in total dyskinesias that lasted for at least 8 weeks, at which time the study was ended. In contrast, a significant increase in levodopa‐induced dyskinesias was observed in the group of animals that had previously received nicotine and were then switched to vehicle. Nicotine treatment did not appear to affect the antiparkinsonian action of levodopa. Interpretation: These data suggest that nicotine or selective nicotinic agonists may represent a useful treatment strategy to reduce levodopa‐induced dyskinesias. Ann Neurol 2007
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DOI: 10.1002/ana.21203
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William Langston</name></author><author><name sortKey="Di Monte, Donato" sort="Di Monte, Donato" uniqKey="Di Monte D" first="Donato" last="Di Monte">Donato Di Monte</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:60434D3A8E9DFA0D6BFD825DCFC2A95648542A2D</idno><date when="2007" year="2007">2007</date><idno type="doi">10.1002/ana.21203</idno><idno type="url">https://api.istex.fr/document/60434D3A8E9DFA0D6BFD825DCFC2A95648542A2D/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002D51</idno><idno type="wicri:Area/Main/Curation">002973</idno><idno type="wicri:Area/Main/Exploration">001002</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Nicotine reduces levodopa‐induced dyskinesias in lesioned monkeys</title><author><name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>The Parkinson's Institute, Sunnyvale</wicri:cityArea></affiliation></author><author><name sortKey="Cox, Heather" sort="Cox, Heather" uniqKey="Cox H" first="Heather" last="Cox">Heather Cox</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>The Parkinson's Institute, Sunnyvale</wicri:cityArea></affiliation></author><author><name sortKey="Parameswaran, Neeraja" sort="Parameswaran, Neeraja" uniqKey="Parameswaran N" first="Neeraja" last="Parameswaran">Neeraja Parameswaran</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>The Parkinson's Institute, Sunnyvale</wicri:cityArea></affiliation></author><author><name sortKey="O Leary, Kathryn" sort="O Leary, Kathryn" uniqKey="O Leary K" first="Kathryn" last="O'Leary">Kathryn O'Leary</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>The Parkinson's Institute, Sunnyvale</wicri:cityArea></affiliation></author><author><name sortKey="Langston, J William" sort="Langston, J William" uniqKey="Langston J" first="J. William" last="Langston">J. William Langston</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>The Parkinson's Institute, Sunnyvale</wicri:cityArea></affiliation></author><author><name sortKey="Di Monte, Donato" sort="Di Monte, Donato" uniqKey="Di Monte D" first="Donato" last="Di Monte">Donato Di Monte</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>The Parkinson's Institute, Sunnyvale</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="sub">Official Journal of the American Neurological Association and the Child Neurology Society</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-12">2007-12</date><biblScope unit="volume">62</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="588">588</biblScope><biblScope unit="page" to="596">596</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">60434D3A8E9DFA0D6BFD825DCFC2A95648542A2D</idno><idno type="DOI">10.1002/ana.21203</idno><idno type="ArticleID">ANA21203</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective: Levodopa, the gold standard for Parkinson's disease treatment, is associated with debilitating abnormal involuntary movements or dyskinesias, for which few treatments are currently available. Studies have implicated numerous neurotransmitters in the development of levodopa‐induced dyskinesias. However, the cholinergic system has received little attention despite an extensive overlap between dopaminergic terminals and cholinergic interneurons in the striatum and the well‐known ability of nicotine to stimulate striatal dopamine release. Our objective, therefore, was to determine whether nicotine treatment reduced levodopa‐induced dyskinesias. Methods: The effect of nicotine (provided in the drinking water) was determined on dyskinesias induced by levodopa (5mg/kg twice daily by oral gavage) in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)–treated monkeys. Results: Nicotine pretreatment reduced peak and total levodopa‐induced dyskinesias in levodopa‐naive monkeys over an 8‐week period, with a decrease in total dyskinesias of about 50%. A crossover study was then done in which levodopa‐treated monkeys originally receiving vehicle were administered nicotine, whereas the levodopa‐treated animals initially receiving nicotine were placed on vehicle. Nicotine treatment to levodopa‐primed monkeys led to an approximately 35% reduction in total dyskinesias that lasted for at least 8 weeks, at which time the study was ended. In contrast, a significant increase in levodopa‐induced dyskinesias was observed in the group of animals that had previously received nicotine and were then switched to vehicle. Nicotine treatment did not appear to affect the antiparkinsonian action of levodopa. Interpretation: These data suggest that nicotine or selective nicotinic agonists may represent a useful treatment strategy to reduce levodopa‐induced dyskinesias. Ann Neurol 2007</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name></region><name sortKey="Cox, Heather" sort="Cox, Heather" uniqKey="Cox H" first="Heather" last="Cox">Heather Cox</name><name sortKey="Di Monte, Donato" sort="Di Monte, Donato" uniqKey="Di Monte D" first="Donato" last="Di Monte">Donato Di Monte</name><name sortKey="Langston, J William" sort="Langston, J William" uniqKey="Langston J" first="J. William" last="Langston">J. William Langston</name><name sortKey="O Leary, Kathryn" sort="O Leary, Kathryn" uniqKey="O Leary K" first="Kathryn" last="O'Leary">Kathryn O'Leary</name><name sortKey="Parameswaran, Neeraja" sort="Parameswaran, Neeraja" uniqKey="Parameswaran N" first="Neeraja" last="Parameswaran">Neeraja Parameswaran</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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