Role of dopaminergic treatment in dopamine receptor down-regulation in advanced Parkinson disease. A positron emission tomographic study
Identifieur interne : 003416 ( Main/Merge ); précédent : 003415; suivant : 003417Role of dopaminergic treatment in dopamine receptor down-regulation in advanced Parkinson disease. A positron emission tomographic study
Auteurs : Stéphane Thobois [France, Royaume-Uni] ; Francois Vingerhoets [Suisse] ; Valerie Fraix [France] ; Jing Xie-Brustolin [France] ; Hélène Mollion [France] ; Nicolas Costes [France] ; Patrick Mertens [France] ; Alim-Louis Benabid [France] ; Pierre Pollak [France] ; Emmanuel Broussolle [France]Source :
- Archives of neurology : (Chicago) [ 0003-9942 ] ; 2004.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Background: In patients with advanced Parkinson disease (PD) who are undergoing long-term treatment with a dopaminergic medication, a down-regulation of striatal dopamine D2 receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration. Objective: To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D2 receptor ligand, in PD patients who completely discontinued dopaminergic therapy (off drug) with that in PD patients who continued receiving dopaminergic therapy (on drug) after undergoing subthalamic nucleus stimulation. Main Outcome Measures: The positron emission tomographic data were acquired in off-stimulation and, for 12 hours, off-medication conditions. Five off-drug PD patients, 7 on-drug PD patients, and 8 healthy subjects participated. Results: In off-drug PD patients, the putaminal raclopride C 11 binding was 24% higher than in on-drug PD patients. The same tendency was noted for the caudate nucleus, but was not significant (P=.07). Compared with control subjects, the putaminal raclopride C 11 binding was increased by 21% in off-drug and was normal in on-drug PD patients. Compared with controls, the caudate raclopride C 11 binding was reduced by 23% in on-drug and was normal in off-drug PD patients. Further analysis using statistical parametric mapping showed a significant increase of binding bilaterally in the caudate nucleus and putamen in off-drug compared with on-drug PD patients (P=.002 at cluster level). Conclusions: The down-regulation of dopamine D2 receptors probably relates to the long-term and intermittent administration of dopaminergic treatments rather than to disease progression. This phenomenon is reversed by the complete withdrawal of dopaminergic drugs. Furthermore, an up-regulation of putaminal dopamine D2 receptors is demonstrated in late-stage PD after dopaminergic drug withdrawal.
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type="wicri:source">INIST</idno><idno type="inist">05-0013551</idno><date when="2004">2004</date><idno type="stanalyst">PASCAL 05-0013551 INIST</idno><idno type="RBID">Pascal:05-0013551</idno><idno type="wicri:Area/PascalFrancis/Corpus">000D44</idno><idno type="wicri:Area/PascalFrancis/Curation">000690</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000C16</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000C16</idno><idno type="wicri:doubleKey">0003-9942:2004:Thobois S:role:of:dopaminergic</idno><idno type="wicri:Area/Main/Merge">003416</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Role of dopaminergic treatment in dopamine receptor down-regulation in advanced Parkinson disease. A positron emission tomographic study</title><author><name sortKey="Thobois, Stephane" sort="Thobois, Stephane" uniqKey="Thobois S" first="Stéphane" last="Thobois">Stéphane Thobois</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Neurological Department D, The Pierre Wertheimer Neurological Hospital and INSERM U 534</s1><s2>Lyon</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Cyclotron Unit (CERMEP), The Pierre Wertheimer Neurological Hospital</s1><s2>Lyon</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Sobell Department of Motor Neurosciences and Movement Disorders, Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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="Vingerhoets, Francois" sort="Vingerhoets, Francois" uniqKey="Vingerhoets F" first="Francois" last="Vingerhoets">Francois Vingerhoets</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Neurological Department, CHUV</s1><s2>Lausanne</s2><s3>CHE</s3><sZ>2 aut.</sZ></inist:fA14><country>Suisse</country><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Fraix, Valerie" sort="Fraix, Valerie" uniqKey="Fraix V" first="Valerie" last="Fraix">Valerie Fraix</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Neurological and Neurosurgical Departments and INSERM U 318, CHU</s1><s2>Grenoble</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Xie Brustolin, Jing" sort="Xie Brustolin, Jing" uniqKey="Xie Brustolin J" first="Jing" last="Xie-Brustolin">Jing Xie-Brustolin</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Neurological Department D, The Pierre Wertheimer Neurological Hospital and INSERM U 534</s1><s2>Lyon</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Mollion, Helene" sort="Mollion, Helene" uniqKey="Mollion H" first="Hélène" last="Mollion">Hélène Mollion</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Neurological Department D, The Pierre Wertheimer Neurological Hospital and INSERM U 534</s1><s2>Lyon</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Costes, Nicolas" sort="Costes, Nicolas" uniqKey="Costes N" first="Nicolas" last="Costes">Nicolas Costes</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Cyclotron Unit (CERMEP), The Pierre Wertheimer Neurological Hospital</s1><s2>Lyon</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Mertens, Patrick" sort="Mertens, Patrick" uniqKey="Mertens P" first="Patrick" last="Mertens">Patrick Mertens</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1> Neurosurgical Department A, The Pierre Wertheimer Neurological Hospital</s1><s2>Lyon</s2><s3>FRA</s3><sZ>7 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Benabid, Alim Louis" sort="Benabid, Alim Louis" uniqKey="Benabid A" first="Alim-Louis" last="Benabid">Alim-Louis Benabid</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Neurological and Neurosurgical Departments and INSERM U 318, CHU</s1><s2>Grenoble</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Pollak, Pierre" sort="Pollak, Pierre" uniqKey="Pollak P" first="Pierre" last="Pollak">Pierre Pollak</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Neurological and Neurosurgical Departments and INSERM U 318, CHU</s1><s2>Grenoble</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Broussolle, Emmanuel" sort="Broussolle, Emmanuel" uniqKey="Broussolle E" first="Emmanuel" last="Broussolle">Emmanuel Broussolle</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Neurological Department D, The Pierre Wertheimer Neurological Hospital and INSERM U 534</s1><s2>Lyon</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Cyclotron Unit (CERMEP), The Pierre Wertheimer Neurological Hospital</s1><s2>Lyon</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Archives of neurology : (Chicago)</title><title level="j" type="abbreviated">Arch. neurol. : (Chic.)</title><idno type="ISSN">0003-9942</idno><imprint><date when="2004">2004</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Archives of neurology : (Chicago)</title><title level="j" type="abbreviated">Arch. neurol. : (Chic.)</title><idno type="ISSN">0003-9942</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Advanced stage</term><term>Dopamine receptor</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Positron</term><term>Tomography</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Système nerveux pathologie</term><term>Traitement</term><term>Récepteur dopaminergique</term><term>Parkinson maladie</term><term>Stade avancé</term><term>Positon</term><term>Tomographie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: In patients with advanced Parkinson disease (PD) who are undergoing long-term treatment with a dopaminergic medication, a down-regulation of striatal dopamine D<sub>2</sub> receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration. Objective: To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D<sub>2</sub> receptor ligand, in PD patients who completely discontinued dopaminergic therapy (off drug) with that in PD patients who continued receiving dopaminergic therapy (on drug) after undergoing subthalamic nucleus stimulation. Main Outcome Measures: The positron emission tomographic data were acquired in off-stimulation and, for 12 hours, off-medication conditions. Five off-drug PD patients, 7 on-drug PD patients, and 8 healthy subjects participated. Results: In off-drug PD patients, the putaminal raclopride C 11 binding was 24% higher than in on-drug PD patients. The same tendency was noted for the caudate nucleus, but was not significant (P=.07). Compared with control subjects, the putaminal raclopride C 11 binding was increased by 21% in off-drug and was normal in on-drug PD patients. Compared with controls, the caudate raclopride C 11 binding was reduced by 23% in on-drug and was normal in off-drug PD patients. Further analysis using statistical parametric mapping showed a significant increase of binding bilaterally in the caudate nucleus and putamen in off-drug compared with on-drug PD patients (P=.002 at cluster level). Conclusions: The down-regulation of dopamine D<sub>2</sub> receptors probably relates to the long-term and intermittent administration of dopaminergic treatments rather than to disease progression. This phenomenon is reversed by the complete withdrawal of dopaminergic drugs. Furthermore, an up-regulation of putaminal dopamine D<sub>2</sub> receptors is demonstrated in late-stage PD after dopaminergic drug withdrawal.</div></front></TEI><affiliations><list><country><li>France</li><li>Royaume-Uni</li><li>Suisse</li></country><region><li>Angleterre</li><li>Auvergne-Rhône-Alpes</li><li>Canton de Vaud</li><li>Grand Londres</li><li>Rhône-Alpes</li></region><settlement><li>Grenoble</li><li>Lausanne</li><li>Londres</li><li>Lyon</li></settlement></list><tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Thobois, Stephane" sort="Thobois, Stephane" uniqKey="Thobois S" first="Stéphane" last="Thobois">Stéphane Thobois</name></region><name sortKey="Benabid, Alim Louis" sort="Benabid, Alim Louis" uniqKey="Benabid A" first="Alim-Louis" last="Benabid">Alim-Louis Benabid</name><name sortKey="Broussolle, Emmanuel" sort="Broussolle, Emmanuel" uniqKey="Broussolle E" first="Emmanuel" last="Broussolle">Emmanuel Broussolle</name><name sortKey="Broussolle, Emmanuel" sort="Broussolle, Emmanuel" uniqKey="Broussolle E" first="Emmanuel" last="Broussolle">Emmanuel Broussolle</name><name sortKey="Costes, Nicolas" sort="Costes, Nicolas" uniqKey="Costes N" first="Nicolas" last="Costes">Nicolas Costes</name><name sortKey="Fraix, Valerie" sort="Fraix, Valerie" uniqKey="Fraix V" first="Valerie" last="Fraix">Valerie Fraix</name><name sortKey="Mertens, Patrick" sort="Mertens, Patrick" uniqKey="Mertens P" first="Patrick" last="Mertens">Patrick Mertens</name><name sortKey="Mollion, Helene" sort="Mollion, Helene" uniqKey="Mollion H" first="Hélène" last="Mollion">Hélène Mollion</name><name sortKey="Pollak, Pierre" sort="Pollak, Pierre" uniqKey="Pollak P" first="Pierre" last="Pollak">Pierre Pollak</name><name sortKey="Thobois, Stephane" sort="Thobois, Stephane" uniqKey="Thobois S" first="Stéphane" last="Thobois">Stéphane Thobois</name><name sortKey="Xie Brustolin, Jing" sort="Xie Brustolin, Jing" uniqKey="Xie Brustolin J" first="Jing" last="Xie-Brustolin">Jing Xie-Brustolin</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Thobois, Stephane" sort="Thobois, Stephane" uniqKey="Thobois S" first="Stéphane" last="Thobois">Stéphane Thobois</name></region></country><country name="Suisse"><region name="Canton de Vaud"><name sortKey="Vingerhoets, Francois" sort="Vingerhoets, Francois" uniqKey="Vingerhoets F" first="Francois" last="Vingerhoets">Francois Vingerhoets</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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