Chronic treatment with MPEP, an mGlu5 receptor antagonist, normalizes basal ganglia glutamate neurotransmission in L-DOPA-treated parkinsonian monkeys.
Identifieur interne : 000946 ( PubMed/Checkpoint ); précédent : 000945; suivant : 000947Chronic treatment with MPEP, an mGlu5 receptor antagonist, normalizes basal ganglia glutamate neurotransmission in L-DOPA-treated parkinsonian monkeys.
Auteurs : Nicolas Morin [Canada] ; Marc Morissette ; Laurent Grégoire ; Baltazar Gomez-Mancilla ; Fabrizio Gasparini ; Thérèse Di PaoloSource :
- Neuropharmacology [ 1873-7064 ] ; 2013.
English descriptors
- KwdEn :
- 2-Amino-5-phosphonovalerate (analogs & derivatives), Amino Acids, Animals, Basal Ganglia (drug effects), Basal Ganglia (metabolism), Corpus Striatum (drug effects), Corpus Striatum (metabolism), Dyskinesia, Drug-Induced (prevention & control), Female, Imidazoles, Levodopa (adverse effects), Macaca fascicularis, Oximes, Parkinsonian Disorders (drug therapy), Parkinsonian Disorders (metabolism), Phenols, Piperidines, Pyridines (pharmacology), Pyridines (therapeutic use), Quinazolines, Radioligand Assay, Receptor, Metabotropic Glutamate 5 (antagonists & inhibitors), Receptor, Metabotropic Glutamate 5 (metabolism), Receptors, AMPA (metabolism), Receptors, N-Methyl-D-Aspartate (metabolism), Tritium, Xanthenes.
- MESH :
- chemical , adverse effects : Levodopa.
- chemical , analogs & derivatives : 2-Amino-5-phosphonovalerate.
- chemical , antagonists & inhibitors : Receptor, Metabotropic Glutamate 5.
- chemical , metabolism : Receptor, Metabotropic Glutamate 5, Receptors, AMPA, Receptors, N-Methyl-D-Aspartate.
- chemical , pharmacology : Pyridines.
- chemical , therapeutic use : Pyridines.
- chemical : Amino Acids, Imidazoles, Oximes, Phenols, Piperidines, Quinazolines, Tritium, Xanthenes.
- drug effects : Basal Ganglia, Corpus Striatum.
- drug therapy : Parkinsonian Disorders.
- metabolism : Basal Ganglia, Corpus Striatum, Parkinsonian Disorders.
- prevention & control : Dyskinesia, Drug-Induced.
- Animals, Female, Macaca fascicularis, Radioligand Assay.
Abstract
Metabotropic glutamate 5 (mGlu5) receptor antagonists reduce L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias (LID) in Parkinson's disease (PD). The aim of this study was to investigate the long-term effect of the prototypal mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) on glutamate receptors known to be involved in the development of LID in the de novo chronic treatment of monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP monkeys were treated for one month with L-DOPA and developed dyskinesias while those treated with L-DOPA and MPEP (10 mg/kg) developed significantly less. Normal control and saline-treated MPTP monkeys were also included. All MPTP monkeys were extensively and similarly denervated. The basal ganglia [(3)H]ABP688 specific binding (mGlu5 receptors) was elevated in L-DOPA-treated MPTP monkeys compared to controls but not in those treated with L-DOPA and MPEP; dyskinesia scores of these monkeys correlated positively with their [(3)H]ABP688 specific binding. Striatal density (B(max)) of [(3)H]ABP688 specific binding increased in L-DOPA-treated MPTP monkeys compared to other groups and affinity (Kd) remained unchanged. Striatal mGlu5 receptor mRNA remained unchanged following treatments. Elevated basal ganglia specific binding of [(3)H]Ro 25-6981 (NMDA NR1/NR2B receptors), [(3)H]Ro 48-8587 (AMPA receptors) but not [(3)H]CGP-39653 (NMDA NR1/NR2A receptors) was observed only in L-DOPA-treated MPTP monkeys; dyskinesias scores correlated with binding. By contrast, basal ganglia [(3)H]LY341495 specific binding (mGlu2/3 receptors) decreased in L-DOPA-treated MPTP monkeys compared to controls, saline and L-DOPA + MPEP treated MPTP monkeys; dyskinesias scores correlated negatively with this binding. Hence, chronic MPEP treatment reduces the development of LID and is associated with a normalization of glutamate neurotransmission.
DOI: 10.1016/j.neuropharm.2013.05.028
PubMed: 23756168
Affiliations:
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xml:lang="en"><term>2-Amino-5-phosphonovalerate (analogs & derivatives)</term><term>Amino Acids</term><term>Animals</term><term>Basal Ganglia (drug effects)</term><term>Basal Ganglia (metabolism)</term><term>Corpus Striatum (drug effects)</term><term>Corpus Striatum (metabolism)</term><term>Dyskinesia, Drug-Induced (prevention & control)</term><term>Female</term><term>Imidazoles</term><term>Levodopa (adverse effects)</term><term>Macaca fascicularis</term><term>Oximes</term><term>Parkinsonian Disorders (drug therapy)</term><term>Parkinsonian Disorders (metabolism)</term><term>Phenols</term><term>Piperidines</term><term>Pyridines (pharmacology)</term><term>Pyridines (therapeutic use)</term><term>Quinazolines</term><term>Radioligand Assay</term><term>Receptor, Metabotropic Glutamate 5 (antagonists & inhibitors)</term><term>Receptor, Metabotropic Glutamate 5 (metabolism)</term><term>Receptors, AMPA (metabolism)</term><term>Receptors, N-Methyl-D-Aspartate (metabolism)</term><term>Tritium</term><term>Xanthenes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>2-Amino-5-phosphonovalerate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Receptor, Metabotropic Glutamate 5</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptor, Metabotropic Glutamate 5</term><term>Receptors, AMPA</term><term>Receptors, N-Methyl-D-Aspartate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Pyridines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Pyridines</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Amino Acids</term><term>Imidazoles</term><term>Oximes</term><term>Phenols</term><term>Piperidines</term><term>Quinazolines</term><term>Tritium</term><term>Xanthenes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Basal Ganglia</term><term>Corpus Striatum</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Basal Ganglia</term><term>Corpus Striatum</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Macaca fascicularis</term><term>Radioligand Assay</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Metabotropic glutamate 5 (mGlu5) receptor antagonists reduce L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias (LID) in Parkinson's disease (PD). The aim of this study was to investigate the long-term effect of the prototypal mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) on glutamate receptors known to be involved in the development of LID in the de novo chronic treatment of monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP monkeys were treated for one month with L-DOPA and developed dyskinesias while those treated with L-DOPA and MPEP (10 mg/kg) developed significantly less. Normal control and saline-treated MPTP monkeys were also included. All MPTP monkeys were extensively and similarly denervated. The basal ganglia [(3)H]ABP688 specific binding (mGlu5 receptors) was elevated in L-DOPA-treated MPTP monkeys compared to controls but not in those treated with L-DOPA and MPEP; dyskinesia scores of these monkeys correlated positively with their [(3)H]ABP688 specific binding. Striatal density (B(max)) of [(3)H]ABP688 specific binding increased in L-DOPA-treated MPTP monkeys compared to other groups and affinity (Kd) remained unchanged. Striatal mGlu5 receptor mRNA remained unchanged following treatments. Elevated basal ganglia specific binding of [(3)H]Ro 25-6981 (NMDA NR1/NR2B receptors), [(3)H]Ro 48-8587 (AMPA receptors) but not [(3)H]CGP-39653 (NMDA NR1/NR2A receptors) was observed only in L-DOPA-treated MPTP monkeys; dyskinesias scores correlated with binding. By contrast, basal ganglia [(3)H]LY341495 specific binding (mGlu2/3 receptors) decreased in L-DOPA-treated MPTP monkeys compared to controls, saline and L-DOPA + MPEP treated MPTP monkeys; dyskinesias scores correlated negatively with this binding. Hence, chronic MPEP treatment reduces the development of LID and is associated with a normalization of glutamate neurotransmission.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23756168</PMID><DateCreated><Year>2013</Year><Month>09</Month><Day>06</Day></DateCreated><DateCompleted><Year>2014</Year><Month>08</Month><Day>13</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-7064</ISSN><JournalIssue CitedMedium="Internet"><Volume>73</Volume><PubDate><Year>2013</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Neuropharmacology</Title><ISOAbbreviation>Neuropharmacology</ISOAbbreviation></Journal><ArticleTitle>Chronic treatment with MPEP, an mGlu5 receptor antagonist, normalizes basal ganglia glutamate neurotransmission in L-DOPA-treated parkinsonian monkeys.</ArticleTitle><Pagination><MedlinePgn>216-31</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.neuropharm.2013.05.028</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0028-3908(13)00242-6</ELocationID><Abstract><AbstractText>Metabotropic glutamate 5 (mGlu5) receptor antagonists reduce L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias (LID) in Parkinson's disease (PD). The aim of this study was to investigate the long-term effect of the prototypal mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) on glutamate receptors known to be involved in the development of LID in the de novo chronic treatment of monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP monkeys were treated for one month with L-DOPA and developed dyskinesias while those treated with L-DOPA and MPEP (10 mg/kg) developed significantly less. Normal control and saline-treated MPTP monkeys were also included. All MPTP monkeys were extensively and similarly denervated. The basal ganglia [(3)H]ABP688 specific binding (mGlu5 receptors) was elevated in L-DOPA-treated MPTP monkeys compared to controls but not in those treated with L-DOPA and MPEP; dyskinesia scores of these monkeys correlated positively with their [(3)H]ABP688 specific binding. Striatal density (B(max)) of [(3)H]ABP688 specific binding increased in L-DOPA-treated MPTP monkeys compared to other groups and affinity (Kd) remained unchanged. Striatal mGlu5 receptor mRNA remained unchanged following treatments. Elevated basal ganglia specific binding of [(3)H]Ro 25-6981 (NMDA NR1/NR2B receptors), [(3)H]Ro 48-8587 (AMPA receptors) but not [(3)H]CGP-39653 (NMDA NR1/NR2A receptors) was observed only in L-DOPA-treated MPTP monkeys; dyskinesias scores correlated with binding. By contrast, basal ganglia [(3)H]LY341495 specific binding (mGlu2/3 receptors) decreased in L-DOPA-treated MPTP monkeys compared to controls, saline and L-DOPA + MPEP treated MPTP monkeys; dyskinesias scores correlated negatively with this binding. Hence, chronic MPEP treatment reduces the development of LID and is associated with a normalization of glutamate neurotransmission.</AbstractText><CopyrightInformation>Copyright © 2013 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Morin</LastName><ForeName>Nicolas</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Laval University Medical Center (CHUQ), Quebec, QC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morissette</LastName><ForeName>Marc</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Grégoire</LastName><ForeName>Laurent</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Gomez-Mancilla</LastName><ForeName>Baltazar</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Gasparini</LastName><ForeName>Fabrizio</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Di Paolo</LastName><ForeName>Thérèse</ForeName><Initials>T</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>06</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Neuropharmacology</MedlineTA><NlmUniqueID>0236217</NlmUniqueID><ISSNLinking>0028-3908</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C510950">3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000596">Amino Acids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007093">Imidazoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C114624">LY 341495</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010091">Oximes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010636">Phenols</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010880">Piperidines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011725">Pyridines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011799">Quinazolines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D064529">Receptor, Metabotropic Glutamate 5</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018091">Receptors, AMPA</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016194">Receptors, N-Methyl-D-Aspartate</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C109643">Ro 25-6981</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C112933">Ro 48-8587</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014966">Xanthenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>10028-17-8</RegistryNumber><NameOfSubstance UI="D014316">Tritium</NameOfSubstance></Chemical><Chemical><RegistryNumber>132472-31-2</RegistryNumber><NameOfSubstance UI="C069052">CGP 39653</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical><Chemical><RegistryNumber>76726-92-6</RegistryNumber><NameOfSubstance UI="D015763">2-Amino-5-phosphonovalerate</NameOfSubstance></Chemical><Chemical><RegistryNumber>7VC0YVI27Y</RegistryNumber><NameOfSubstance UI="C121465">6-methyl-2-(phenylethynyl)pyridine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D015763" MajorTopicYN="N">2-Amino-5-phosphonovalerate</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000596" MajorTopicYN="N">Amino Acids</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001479" MajorTopicYN="N">Basal Ganglia</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003342" MajorTopicYN="N">Corpus Striatum</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004409" MajorTopicYN="N">Dyskinesia, Drug-Induced</DescriptorName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007093" MajorTopicYN="N">Imidazoles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007980" MajorTopicYN="N">Levodopa</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008252" MajorTopicYN="N">Macaca fascicularis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010091" MajorTopicYN="N">Oximes</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020734" MajorTopicYN="N">Parkinsonian Disorders</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010636" MajorTopicYN="N">Phenols</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010880" MajorTopicYN="N">Piperidines</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011725" MajorTopicYN="N">Pyridines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011799" MajorTopicYN="N">Quinazolines</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011869" MajorTopicYN="N">Radioligand Assay</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D064529" MajorTopicYN="N">Receptor, Metabotropic Glutamate 5</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018091" MajorTopicYN="N">Receptors, AMPA</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016194" MajorTopicYN="N">Receptors, N-Methyl-D-Aspartate</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014316" MajorTopicYN="N">Tritium</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014966" MajorTopicYN="N">Xanthenes</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine</Keyword><Keyword MajorTopicYN="N">2-methyl-6-(phenylethynyl)pyridine</Keyword><Keyword MajorTopicYN="N">3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine</Keyword><Keyword MajorTopicYN="N">6-OHDA</Keyword><Keyword MajorTopicYN="N">6-hydroxydopamine</Keyword><Keyword MajorTopicYN="N">AMPA</Keyword><Keyword MajorTopicYN="N">AMPA receptor</Keyword><Keyword MajorTopicYN="N">B(max)</Keyword><Keyword MajorTopicYN="N">DA</Keyword><Keyword MajorTopicYN="N">DL</Keyword><Keyword MajorTopicYN="N">DM</Keyword><Keyword MajorTopicYN="N">GP</Keyword><Keyword MajorTopicYN="N">GPe</Keyword><Keyword MajorTopicYN="N">GPi</Keyword><Keyword MajorTopicYN="N">K(d)</Keyword><Keyword MajorTopicYN="N">LID</Keyword><Keyword MajorTopicYN="N">MPEP</Keyword><Keyword MajorTopicYN="N">MPTP</Keyword><Keyword MajorTopicYN="N">MTEP</Keyword><Keyword MajorTopicYN="N">N-methyl-d-aspartate</Keyword><Keyword MajorTopicYN="N">NMDA</Keyword><Keyword MajorTopicYN="N">NMDA receptor</Keyword><Keyword MajorTopicYN="N">PD</Keyword><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">VL</Keyword><Keyword MajorTopicYN="N">VM</Keyword><Keyword MajorTopicYN="N">affinity</Keyword><Keyword MajorTopicYN="N">density</Keyword><Keyword MajorTopicYN="N">dopamine</Keyword><Keyword MajorTopicYN="N">dorsolateral</Keyword><Keyword MajorTopicYN="N">dorsomedial</Keyword><Keyword MajorTopicYN="N">external globus pallidus</Keyword><Keyword MajorTopicYN="N">globus pallidus</Keyword><Keyword MajorTopicYN="N">internal globus pallidus</Keyword><Keyword MajorTopicYN="N">l-3,4-dihydroxyphenylalanine</Keyword><Keyword MajorTopicYN="N">l-DOPA</Keyword><Keyword MajorTopicYN="N">l-DOPA-induced dyskinesias</Keyword><Keyword MajorTopicYN="N">mGlu</Keyword><Keyword MajorTopicYN="N">mGlu2/3 receptor</Keyword><Keyword MajorTopicYN="N">mGlu5 receptor</Keyword><Keyword MajorTopicYN="N">metabotropic glutamate</Keyword><Keyword MajorTopicYN="N">ventrolateral</Keyword><Keyword MajorTopicYN="N">ventromedial</Keyword><Keyword MajorTopicYN="N">α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2012</Year><Month>10</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2013</Year><Month>05</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2013</Year><Month>05</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>6</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>6</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>8</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23756168</ArticleId><ArticleId IdType="pii">S0028-3908(13)00242-6</ArticleId><ArticleId IdType="doi">10.1016/j.neuropharm.2013.05.028</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><name sortKey="Gasparini, Fabrizio" sort="Gasparini, Fabrizio" uniqKey="Gasparini F" first="Fabrizio" last="Gasparini">Fabrizio Gasparini</name><name sortKey="Gomez Mancilla, Baltazar" sort="Gomez Mancilla, Baltazar" uniqKey="Gomez Mancilla B" first="Baltazar" last="Gomez-Mancilla">Baltazar Gomez-Mancilla</name><name sortKey="Gregoire, Laurent" sort="Gregoire, Laurent" uniqKey="Gregoire L" first="Laurent" last="Grégoire">Laurent Grégoire</name><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name></noCountry><country name="Canada"><noRegion><name sortKey="Morin, Nicolas" sort="Morin, Nicolas" uniqKey="Morin N" first="Nicolas" last="Morin">Nicolas Morin</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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