Beginning‐of‐dose and rebound worsening in MPTP‐treated common marmosets treated with levodopa
Identifieur interne : 006569 ( Main/Merge ); précédent : 006568; suivant : 006570Beginning‐of‐dose and rebound worsening in MPTP‐treated common marmosets treated with levodopa
Auteurs : Mikko Kuoppam Ki [Royaume-Uni] ; Ghassan Al-Barghouthy [Royaume-Uni] ; Michael Jackson [Royaume-Uni] ; Lance Smith [Royaume-Uni] ; Bai-Yun Zeng [Royaume-Uni] ; Niall Quinn [Royaume-Uni] ; Peter Jenner [Royaume-Uni]Source :
- Movement Disorders [ 0885-3185 ] ; 2002-11.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Callithrix, Disease Models, Animal, Dose-Response Relationship, Drug, Dyskinesia, Drug-Induced (physiopathology), Female, Levodopa (toxicity), L‐dopa, MPTP, Male, Motor Activity (drug effects), Motor Skills (drug effects), Neurologic Examination (drug effects), Parkinson's disease, Parkinsonian Disorders (chemically induced), Parkinsonian Disorders (physiopathology), Recurrence, dyskinesia, motor complication.
- MESH :
- chemical , toxicity : Levodopa.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemically induced : Parkinsonian Disorders.
- drug effects : Motor Activity, Motor Skills, Neurologic Examination.
- physiopathology : Dyskinesia, Drug-Induced, Parkinsonian Disorders.
- Animals, Callithrix, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Male, Recurrence.
Abstract
A wide range of motor fluctuations develop in Parkinson's disease (PD) patients after prolonged levodopa (L‐dopa) treatment, but few experimental models exist in which these can be investigated. We report on motor fluctuations occurring in MPTP‐treated common marmosets (Callithrix jacchus) treated repeatedly with L‐dopa. All animals showed an improvement in motor function in response to L‐dopa, and rapidly developed peak‐dose dyskinesia. During the period of L‐dopa action, brief periods of immobility were occasionally observed. After acute L‐dopa challenge, animals exhibited a worsening of motor function before improvement, and after the beneficial response to L‐dopa declined, motor performance showed rebound worsening to below‐baseline values. Before L‐dopa challenge and during wearing‐off and rebound worsening, leg dystonias were observed. Although these findings cannot necessarily be generalized to all MPTP‐treated nonhuman primates, they demonstrate that MPTP‐treated marmosets show a range of different motor fluctuations analogous to those seen in PD patients chronically treated with L‐dopa. Therefore, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated primates can provide a model in which the pathophysiology of treatment complications can be investigated. © 2002 Movement Disorder Society
Url:
DOI: 10.1002/mds.10263
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<front><div type="abstract" xml:lang="en">A wide range of motor fluctuations develop in Parkinson's disease (PD) patients after prolonged levodopa (L‐dopa) treatment, but few experimental models exist in which these can be investigated. We report on motor fluctuations occurring in MPTP‐treated common marmosets (Callithrix jacchus) treated repeatedly with L‐dopa. All animals showed an improvement in motor function in response to L‐dopa, and rapidly developed peak‐dose dyskinesia. During the period of L‐dopa action, brief periods of immobility were occasionally observed. After acute L‐dopa challenge, animals exhibited a worsening of motor function before improvement, and after the beneficial response to L‐dopa declined, motor performance showed rebound worsening to below‐baseline values. Before L‐dopa challenge and during wearing‐off and rebound worsening, leg dystonias were observed. Although these findings cannot necessarily be generalized to all MPTP‐treated nonhuman primates, they demonstrate that MPTP‐treated marmosets show a range of different motor fluctuations analogous to those seen in PD patients chronically treated with L‐dopa. Therefore, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated primates can provide a model in which the pathophysiology of treatment complications can be investigated. © 2002 Movement Disorder Society</div>
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<front><div type="abstract" xml:lang="en">A wide range of motor fluctuations develop in Parkinson's disease (PD) patients after prolonged levodopa (L‐dopa) treatment, but few experimental models exist in which these can be investigated. We report on motor fluctuations occurring in MPTP‐treated common marmosets (Callithrix jacchus) treated repeatedly with L‐dopa. All animals showed an improvement in motor function in response to L‐dopa, and rapidly developed peak‐dose dyskinesia. During the period of L‐dopa action, brief periods of immobility were occasionally observed. After acute L‐dopa challenge, animals exhibited a worsening of motor function before improvement, and after the beneficial response to L‐dopa declined, motor performance showed rebound worsening to below‐baseline values. Before L‐dopa challenge and during wearing‐off and rebound worsening, leg dystonias were observed. Although these findings cannot necessarily be generalized to all MPTP‐treated nonhuman primates, they demonstrate that MPTP‐treated marmosets show a range of different motor fluctuations analogous to those seen in PD patients chronically treated with L‐dopa. Therefore, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated primates can provide a model in which the pathophysiology of treatment complications can be investigated. © 2002 Movement Disorder Society</div>
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<PubMed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Beginning-of-dose and rebound worsening in MPTP-treated common marmosets treated with levodopa.</title>
<author><name sortKey="Kuoppam Ki, Mikko" sort="Kuoppam Ki, Mikko" uniqKey="Kuoppam Ki M" first="Mikko" last="Kuoppam Ki">Mikko Kuoppam Ki</name>
<affiliation wicri:level="3"><nlm:affiliation>Neurodegenerative Diseases Research Centre, King's College, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Neurodegenerative Diseases Research Centre, King's College, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Al Barghouthy, Ghassan" sort="Al Barghouthy, Ghassan" uniqKey="Al Barghouthy G" first="Ghassan" last="Al-Barghouthy">Ghassan Al-Barghouthy</name>
</author>
<author><name sortKey="Jackson, Michael" sort="Jackson, Michael" uniqKey="Jackson M" first="Michael" last="Jackson">Michael Jackson</name>
</author>
<author><name sortKey="Smith, Lance" sort="Smith, Lance" uniqKey="Smith L" first="Lance" last="Smith">Lance Smith</name>
</author>
<author><name sortKey="Zeng, Bai Yun" sort="Zeng, Bai Yun" uniqKey="Zeng B" first="Bai-Yun" last="Zeng">Bai-Yun Zeng</name>
</author>
<author><name sortKey="Quinn, Niall" sort="Quinn, Niall" uniqKey="Quinn N" first="Niall" last="Quinn">Niall Quinn</name>
</author>
<author><name sortKey="Jenner, Peter" sort="Jenner, Peter" uniqKey="Jenner P" first="Peter" last="Jenner">Peter Jenner</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2002">2002</date>
<idno type="RBID">pubmed:12465074</idno>
<idno type="pmid">12465074</idno>
<idno type="doi">10.1002/mds.10263</idno>
<idno type="wicri:Area/PubMed/Corpus">003905</idno>
<idno type="wicri:Area/PubMed/Curation">003905</idno>
<idno type="wicri:Area/PubMed/Checkpoint">003B85</idno>
<idno type="wicri:Area/Ncbi/Merge">000946</idno>
<idno type="wicri:Area/Ncbi/Curation">000946</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000946</idno>
<idno type="wicri:doubleKey">0885-3185:2002:Kuoppam Ki M:beginning:of:dose</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Beginning-of-dose and rebound worsening in MPTP-treated common marmosets treated with levodopa.</title>
<author><name sortKey="Kuoppam Ki, Mikko" sort="Kuoppam Ki, Mikko" uniqKey="Kuoppam Ki M" first="Mikko" last="Kuoppam Ki">Mikko Kuoppam Ki</name>
<affiliation wicri:level="3"><nlm:affiliation>Neurodegenerative Diseases Research Centre, King's College, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Neurodegenerative Diseases Research Centre, King's College, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Al Barghouthy, Ghassan" sort="Al Barghouthy, Ghassan" uniqKey="Al Barghouthy G" first="Ghassan" last="Al-Barghouthy">Ghassan Al-Barghouthy</name>
</author>
<author><name sortKey="Jackson, Michael" sort="Jackson, Michael" uniqKey="Jackson M" first="Michael" last="Jackson">Michael Jackson</name>
</author>
<author><name sortKey="Smith, Lance" sort="Smith, Lance" uniqKey="Smith L" first="Lance" last="Smith">Lance Smith</name>
</author>
<author><name sortKey="Zeng, Bai Yun" sort="Zeng, Bai Yun" uniqKey="Zeng B" first="Bai-Yun" last="Zeng">Bai-Yun Zeng</name>
</author>
<author><name sortKey="Quinn, Niall" sort="Quinn, Niall" uniqKey="Quinn N" first="Niall" last="Quinn">Niall Quinn</name>
</author>
<author><name sortKey="Jenner, Peter" sort="Jenner, Peter" uniqKey="Jenner P" first="Peter" last="Jenner">Peter Jenner</name>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="ISSN">0885-3185</idno>
<imprint><date when="2002" type="published">2002</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term>
<term>Animals</term>
<term>Callithrix</term>
<term>Disease Models, Animal</term>
<term>Dose-Response Relationship, Drug</term>
<term>Dyskinesia, Drug-Induced (physiopathology)</term>
<term>Female</term>
<term>Levodopa (toxicity)</term>
<term>Male</term>
<term>Motor Activity (drug effects)</term>
<term>Motor Skills (drug effects)</term>
<term>Neurologic Examination (drug effects)</term>
<term>Parkinsonian Disorders (chemically induced)</term>
<term>Parkinsonian Disorders (physiopathology)</term>
<term>Recurrence</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Levodopa</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term>
</keywords>
<keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinsonian Disorders</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Motor Activity</term>
<term>Motor Skills</term>
<term>Neurologic Examination</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term>
<term>Parkinsonian Disorders</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Callithrix</term>
<term>Disease Models, Animal</term>
<term>Dose-Response Relationship, Drug</term>
<term>Female</term>
<term>Male</term>
<term>Recurrence</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">A wide range of motor fluctuations develop in Parkinson's disease (PD) patients after prolonged levodopa (L-dopa) treatment, but few experimental models exist in which these can be investigated. We report on motor fluctuations occurring in MPTP-treated common marmosets (Callithrix jacchus) treated repeatedly with L-dopa. All animals showed an improvement in motor function in response to L-dopa, and rapidly developed peak-dose dyskinesia. During the period of L-dopa action, brief periods of immobility were occasionally observed. After acute L-dopa challenge, animals exhibited a worsening of motor function before improvement, and after the beneficial response to L-dopa declined, motor performance showed rebound worsening to below-baseline values. Before L-dopa challenge and during wearing-off and rebound worsening, leg dystonias were observed. Although these findings cannot necessarily be generalized to all MPTP-treated nonhuman primates, they demonstrate that MPTP-treated marmosets show a range of different motor fluctuations analogous to those seen in PD patients chronically treated with L-dopa. Therefore, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates can provide a model in which the pathophysiology of treatment complications can be investigated.</div>
</front>
</TEI>
</PubMed>
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