Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high‐dose levodopa in the reserpine‐treated rat model of Parkinson's disease
Identifieur interne : 000249 ( Istex/Corpus ); précédent : 000248; suivant : 000250Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high‐dose levodopa in the reserpine‐treated rat model of Parkinson's disease
Auteurs : Gregorio Segovia ; Francisco Mora ; Alan R. Crossman ; Jonathan M. BrotchieSource :
- Movement Disorders [ 0885-3185 ] ; 2003-02.
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- KwdEn :
Abstract
The present study was designed to determine the potential of CB1 cannabinoid receptor modulating compounds in the treatment of L‐3,4‐dihydroxyphenylalanine (L‐dopa)–induced dyskinesia in Parkinson's disease. In the reserpine‐treated rat model of parkinsonism, administration of a high dose of L‐dopa (150 mg/kg) but not of Cl‐APB (0.5 mg/kg) or quinpirole (0.5 mg/kg) produced a hyperkinetic state characterised by an increase in horizontal and vertical activity, which likely represent correlates of antiparkinsonian and dyskinetic activity, respectively. Injection of the CB1 cannabinoid receptor antagonist SR141716 (0.1–3 mg/kg) reduced the increase in vertical activity elicited by L‐dopa without affecting the increase in horizontal activity. Injection of the CB1 cannabinoid receptor agonist WIN55,212‐2 (0.1–3 mg/kg) reduced the L‐dopa–induced increase in vertical activity and, at the highest dose only (3 mg/kg), also reduced horizontal activity elicited by L‐dopa. WIN55,212‐2 (1 mg/kg) reduced motor activity induced by both the D1 receptor agonist Cl‐APB (0.5 mg/kg) and the D2 receptor agonist quinpirole (0.5 mg/kg) in the reserpine‐treated rat. SR141716 (1 mg/kg) had no effects on motor activity induced by Cl‐APB (0.5 mg/kg) nor quinpirole (0.5 mg/kg) in the reserpine‐treated rat. Injection of the inhibitor of endocannabinoid transport AM404 (0.1–1 mg/kg) did not affect the increase in horizontal or vertical activity elicited by L‐dopa (150 mg/kg) in the reserpine‐treated rat. The data suggest that both CB1 cannabinoid receptor antagonists and agonists can modulate the behavioural effects of L‐dopa and may be useful for the treatment of the dyskinesia associated with long‐term L‐dopa treatment of Parkinson's disease. © 2002 Movement Disorder Society
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DOI: 10.1002/mds.10312
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In the reserpine‐treated rat model of parkinsonism, administration of a high dose of L‐dopa (150 mg/kg) but not of Cl‐APB (0.5 mg/kg) or quinpirole (0.5 mg/kg) produced a hyperkinetic state characterised by an increase in horizontal and vertical activity, which likely represent correlates of antiparkinsonian and dyskinetic activity, respectively. Injection of the CB1 cannabinoid receptor antagonist SR141716 (0.1–3 mg/kg) reduced the increase in vertical activity elicited by L‐dopa without affecting the increase in horizontal activity. Injection of the CB1 cannabinoid receptor agonist WIN55,212‐2 (0.1–3 mg/kg) reduced the L‐dopa–induced increase in vertical activity and, at the highest dose only (3 mg/kg), also reduced horizontal activity elicited by L‐dopa. WIN55,212‐2 (1 mg/kg) reduced motor activity induced by both the D1 receptor agonist Cl‐APB (0.5 mg/kg) and the D2 receptor agonist quinpirole (0.5 mg/kg) in the reserpine‐treated rat. SR141716 (1 mg/kg) had no effects on motor activity induced by Cl‐APB (0.5 mg/kg) nor quinpirole (0.5 mg/kg) in the reserpine‐treated rat. Injection of the inhibitor of endocannabinoid transport AM404 (0.1–1 mg/kg) did not affect the increase in horizontal or vertical activity elicited by L‐dopa (150 mg/kg) in the reserpine‐treated rat. The data suggest that both CB1 cannabinoid receptor antagonists and agonists can modulate the behavioural effects of L‐dopa and may be useful for the treatment of the dyskinesia associated with long‐term L‐dopa treatment of Parkinson's disease. © 2002 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Gregorio Segovia PhD</name><affiliations><json:string>Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, United Kingdom</json:string><json:string>Department of Physiology, Faculty of Medicine, Universidad Complutense, Madrid, Spain</json:string></affiliations></json:item><json:item><name>Francisco Mora MD, PhD</name><affiliations><json:string>Department of Physiology, Faculty of Medicine, Universidad Complutense, Madrid, Spain</json:string></affiliations></json:item><json:item><name>Alan R. 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SR141716 (1 mg/kg) had no effects on motor activity induced by Cl‐APB (0.5 mg/kg) nor quinpirole (0.5 mg/kg) in the reserpine‐treated rat. Injection of the inhibitor of endocannabinoid transport AM404 (0.1–1 mg/kg) did not affect the increase in horizontal or vertical activity elicited by L‐dopa (150 mg/kg) in the reserpine‐treated rat. 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SR141716 (1 mg/kg) had no effects on motor activity induced by Cl‐APB (0.5 mg/kg) nor quinpirole (0.5 mg/kg) in the reserpine‐treated rat. Injection of the inhibitor of endocannabinoid transport AM404 (0.1–1 mg/kg) did not affect the increase in horizontal or vertical activity elicited by L‐dopa (150 mg/kg) in the reserpine‐treated rat. 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In the reserpine‐treated rat model of parkinsonism, administration of a high dose of <sc>L</sc>‐dopa (150 mg/kg) but not of Cl‐APB (0.5 mg/kg) or quinpirole (0.5 mg/kg) produced a hyperkinetic state characterised by an increase in horizontal and vertical activity, which likely represent correlates of antiparkinsonian and dyskinetic activity, respectively. Injection of the CB1 cannabinoid receptor antagonist SR141716 (0.1–3 mg/kg) reduced the increase in vertical activity elicited by <sc>L</sc>‐dopa without affecting the increase in horizontal activity. Injection of the CB1 cannabinoid receptor agonist WIN55,212‐2 (0.1–3 mg/kg) reduced the <sc>L</sc>‐dopa–induced increase in vertical activity and, at the highest dose only (3 mg/kg), also reduced horizontal activity elicited by <sc>L</sc>‐dopa. WIN55,212‐2 (1 mg/kg) reduced motor activity induced by both the D1 receptor agonist Cl‐APB (0.5 mg/kg) and the D2 receptor agonist quinpirole (0.5 mg/kg) in the reserpine‐treated rat. SR141716 (1 mg/kg) had no effects on motor activity induced by Cl‐APB (0.5 mg/kg) nor quinpirole (0.5 mg/kg) in the reserpine‐treated rat. Injection of the inhibitor of endocannabinoid transport AM404 (0.1–1 mg/kg) did not affect the increase in horizontal or vertical activity elicited by <sc>L</sc>‐dopa (150 mg/kg) in the reserpine‐treated rat. The data suggest that both CB1 cannabinoid receptor antagonists and agonists can modulate the behavioural effects of <sc>L</sc>‐dopa and may be useful for the treatment of the dyskinesia associated with long‐term <sc>L</sc>‐dopa treatment of Parkinson's disease. © 2002 Movement Disorder Society</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 3-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high‐dose levodopa in the reserpine‐treated rat model of Parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Cannabinoid Compounds, L‐dopa, and Hyperkinesia</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high‐dose levodopa in the reserpine‐treated rat model of Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Gregorio</namePart><namePart type="family">Segovia</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, United Kingdom</affiliation><affiliation>Department of Physiology, Faculty of Medicine, Universidad Complutense, Madrid, Spain</affiliation><description>Correspondence: Department of Physiology, Faculty of Medicine, Universidad Complutense, Ciudad Universitaria, s/n, 28040 Madrid, Spain</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Francisco</namePart><namePart type="family">Mora</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Physiology, Faculty of Medicine, Universidad Complutense, Madrid, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alan R.</namePart><namePart type="family">Crossman</namePart><namePart type="termsOfAddress">DSc</namePart><affiliation>Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, United Kingdom</affiliation><affiliation>Motac Neuroscience Ltd., Manchester Science Park, Manchester, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jonathan M.</namePart><namePart type="family">Brotchie</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, United Kingdom</affiliation><affiliation>Motac Neuroscience Ltd., Manchester Science Park, Manchester, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">2003-02</dateIssued><dateCaptured encoding="w3cdtf">2002-02-01</dateCaptured><dateValid encoding="w3cdtf">2002-07-10</dateValid><copyrightDate encoding="w3cdtf">2003</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">7</extent><extent unit="tables">1</extent><extent unit="references">49</extent><extent unit="words">5442</extent></physicalDescription><abstract lang="en">The present study was designed to determine the potential of CB1 cannabinoid receptor modulating compounds in the treatment of L‐3,4‐dihydroxyphenylalanine (L‐dopa)–induced dyskinesia in Parkinson's disease. In the reserpine‐treated rat model of parkinsonism, administration of a high dose of L‐dopa (150 mg/kg) but not of Cl‐APB (0.5 mg/kg) or quinpirole (0.5 mg/kg) produced a hyperkinetic state characterised by an increase in horizontal and vertical activity, which likely represent correlates of antiparkinsonian and dyskinetic activity, respectively. Injection of the CB1 cannabinoid receptor antagonist SR141716 (0.1–3 mg/kg) reduced the increase in vertical activity elicited by L‐dopa without affecting the increase in horizontal activity. Injection of the CB1 cannabinoid receptor agonist WIN55,212‐2 (0.1–3 mg/kg) reduced the L‐dopa–induced increase in vertical activity and, at the highest dose only (3 mg/kg), also reduced horizontal activity elicited by L‐dopa. WIN55,212‐2 (1 mg/kg) reduced motor activity induced by both the D1 receptor agonist Cl‐APB (0.5 mg/kg) and the D2 receptor agonist quinpirole (0.5 mg/kg) in the reserpine‐treated rat. SR141716 (1 mg/kg) had no effects on motor activity induced by Cl‐APB (0.5 mg/kg) nor quinpirole (0.5 mg/kg) in the reserpine‐treated rat. Injection of the inhibitor of endocannabinoid transport AM404 (0.1–1 mg/kg) did not affect the increase in horizontal or vertical activity elicited by L‐dopa (150 mg/kg) in the reserpine‐treated rat. The data suggest that both CB1 cannabinoid receptor antagonists and agonists can modulate the behavioural effects of L‐dopa and may be useful for the treatment of the dyskinesia associated with long‐term L‐dopa treatment of Parkinson's disease. © 2002 Movement Disorder Society</abstract><note type="funding">Medical Research Council (UK)</note><note type="funding">Comunidad Autónoma de Madrid (Spain)</note><subject lang="en"><genre>Keywords</genre><topic>CB1 receptors</topic><topic>cannabinoids</topic><topic>L‐dopa</topic><topic>dyskinesia</topic><topic>reserpine</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title><subTitle>Official Journal of the Movement Disorder Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2003</date><detail type="volume"><caption>vol.</caption><number>18</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>138</start><end>149</end><total>12</total></extent></part></relatedItem><identifier type="istex">E717F6FBFBFE610C70E9A45BF13EE32A44CB41DA</identifier><identifier type="DOI">10.1002/mds.10312</identifier><identifier type="ArticleID">MDS10312</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2003 Movement Disorders Society</accessCondition><recordInfo><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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