Alteration of glutamate receptors in the striatum of dyskinetic 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys following dopamine agonist treatment
Identifieur interne : 003103 ( Main/Exploration ); précédent : 003102; suivant : 003104Alteration of glutamate receptors in the striatum of dyskinetic 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys following dopamine agonist treatment
Auteurs : Frédéric Calon [Canada] ; Marc Morissette [Canada] ; Othman Ghribi [Canada] ; Martin Goulet [Canada] ; Richard Grondin [Canada] ; Pierre J. Blanchet [Canada] ; Paul J. Bedard [Canada] ; Thérèse Di Paolo [Canada]Source :
- Progress in neuro-psychopharmacology & biological psychiatry [ 0278-5846 ] ; 2002.
Descripteurs français
- Pascal (Inist)
- Corps strié, Modèle animal, Dyskinésie, Animal, Singe, Encéphale, Système nerveux central, Récepteur glutamate, Récepteur dopaminergique D2, Récepteur dopaminergique D1, Agoniste, Antagoniste, Récepteur AMPA, Récepteur NMDA, Interaction moléculaire, Pathogénie, Transmission glutamatergique, Glycine, Pyridine(1-méthyl-4-phényl-1,2,3,6-tétrahydro), Toxicité, Glutamate, Glutamine.
- Wicri :
- topic : Singe.
English descriptors
- KwdEn :
- AMPA receptor, Agonist, Animal, Animal model, Antagonist, Brain (vertebrata), Central nervous system, Corpus striatum, D1 Dopamine receptor, D2 Dopamine receptor, Dyskinesia, Glutamate, Glutamate receptor, Glutamatergic transmission, Glutamine, Glycine, Molecular interaction, Monkey, NMDA receptor, Pathogenesis, Toxicity.
Abstract
The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal lesion and dopaminomimetic treatment on parameters of glutamatergic activity within the basal ganglia of monkeys were studied in relation with the development of dyskinesias. Drug-naive controls, saline-treated MPTP monkeys, as well as MPTP monkeys treated with either a long-acting D2 agonist (cabergoline) or a D1 agonist (SKF-82958) given by intermittent injections or continuous infusion, were included in this study. 3H-L-glutamate, 3H-α-amino-3-hydroxy-5-methylisoxasole-4-propionate (AMPA), 3H-glycine, 3H-CGP39653 (an N-methyl-D-aspartate, NMDA, antagonist selective for NR1/NR2A assembly) and 3H-Ro 25-6981 (an NMDA antagonist selective for NR1/NR2B assembly), specific binding to glutamate receptors, the expression of the NR1 subunit of NMDA receptors and glutamate, glutamine and glycine concentrations were studied by autoradiography, in situ hybridization and high-performance liquid chromatography (HPLC), respectively. Pulsatile SKF-82958 and cabergoline treatment relieved parkinsonian symptoms, whereas animals continuously treated with SKF-82958 remained akinetic. Pulsatile SKF-82958 induced dyskinesias in two of the three animals tested, whereas cabergoline did not. MPTP induced no significant changes of striatal specific binding of the radioligands used, NR1 mRNA expression and amino acid concentrations. In the putamen, pulsatile SKF-82958 treatment was associated with decreased content of glycine and glutamate, whereas only glycine was decreased in cabergoline-treated monkeys. Cabergoline and continuous administration of SKF-82958 led to lower levels of NR1 mRNA in the caudate in comparison to pulsatile SKF-82958 administration. The development of dyskinesias following a D1 agonist treatment was associated with an upregulation of 3H-glutamate [+49%], 3H-AMPA [+38%], 3H-CGP39653 [+111%], 3H-glycine [+26%, nonsignificant] and 3H-Ro 25-6981 [+33%] specific binding in the striatum in comparison to nondyskinetic MPTP monkeys. Our data suggest that supersensitivity to glutamatergic input in the striatum might play a role in the pathogenesis of dopaminomimetic-induced dyskinesias and further support the therapeutic potential of glutamate antagonists in Parkinson's disease.
Affiliations:
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Bedard</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research Unit, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">02-0226511</idno><date when="2002">2002</date><idno type="stanalyst">PASCAL 02-0226511 INIST</idno><idno type="RBID">Pascal:02-0226511</idno><idno type="wicri:Area/PascalFrancis/Corpus">000B91</idno><idno type="wicri:Area/PascalFrancis/Curation">000132</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000A43</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000A43</idno><idno type="wicri:doubleKey">0278-5846:2002:Calon F:alteration:of:glutamate</idno><idno type="wicri:Area/Main/Merge">003552</idno><idno type="wicri:Area/Main/Curation">003103</idno><idno type="wicri:Area/Main/Exploration">003103</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Alteration of glutamate receptors in the striatum of dyskinetic 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys following dopamine agonist treatment</title><author><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Ghribi, Othman" sort="Ghribi, Othman" uniqKey="Ghribi O" first="Othman" last="Ghribi">Othman Ghribi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research Unit, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Goulet, Martin" sort="Goulet, Martin" uniqKey="Goulet M" first="Martin" last="Goulet">Martin Goulet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Grondin, Richard" sort="Grondin, Richard" uniqKey="Grondin R" first="Richard" last="Grondin">Richard Grondin</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research Unit, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research Unit, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research Unit, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL)</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Quebec, Quebec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, Quebec</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Progress in neuro-psychopharmacology & biological psychiatry</title><title level="j" type="abbreviated">Prog. neuro-psychopharmacol. biol. psychiatr.</title><idno type="ISSN">0278-5846</idno><imprint><date when="2002">2002</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Progress in neuro-psychopharmacology & biological psychiatry</title><title level="j" type="abbreviated">Prog. neuro-psychopharmacol. biol. psychiatr.</title><idno type="ISSN">0278-5846</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMPA receptor</term><term>Agonist</term><term>Animal</term><term>Animal model</term><term>Antagonist</term><term>Brain (vertebrata)</term><term>Central nervous system</term><term>Corpus striatum</term><term>D1 Dopamine receptor</term><term>D2 Dopamine receptor</term><term>Dyskinesia</term><term>Glutamate</term><term>Glutamate receptor</term><term>Glutamatergic transmission</term><term>Glutamine</term><term>Glycine</term><term>Molecular interaction</term><term>Monkey</term><term>NMDA receptor</term><term>Pathogenesis</term><term>Toxicity</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Corps strié</term><term>Modèle animal</term><term>Dyskinésie</term><term>Animal</term><term>Singe</term><term>Encéphale</term><term>Système nerveux central</term><term>Récepteur glutamate</term><term>Récepteur dopaminergique D2</term><term>Récepteur dopaminergique D1</term><term>Agoniste</term><term>Antagoniste</term><term>Récepteur AMPA</term><term>Récepteur NMDA</term><term>Interaction moléculaire</term><term>Pathogénie</term><term>Transmission glutamatergique</term><term>Glycine</term><term>Pyridine(1-méthyl-4-phényl-1,2,3,6-tétrahydro)</term><term>Toxicité</term><term>Glutamate</term><term>Glutamine</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Singe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal lesion and dopaminomimetic treatment on parameters of glutamatergic activity within the basal ganglia of monkeys were studied in relation with the development of dyskinesias. Drug-naive controls, saline-treated MPTP monkeys, as well as MPTP monkeys treated with either a long-acting D<sub>2</sub> agonist (cabergoline) or a D<sub>1</sub> agonist (SKF-82958) given by intermittent injections or continuous infusion, were included in this study. <sup>3</sup>H-L-glutamate, <sup>3</sup>H-α-amino-3-hydroxy-5-methylisoxasole-4-propionate (AMPA), <sup>3</sup>H-glycine, <sup>3</sup>H-CGP39653 (an N-methyl-D-aspartate, NMDA, antagonist selective for NR1/NR2A assembly) and <sup>3</sup>H-Ro 25-6981 (an NMDA antagonist selective for NR1/NR2B assembly), specific binding to glutamate receptors, the expression of the NR1 subunit of NMDA receptors and glutamate, glutamine and glycine concentrations were studied by autoradiography, in situ hybridization and high-performance liquid chromatography (HPLC), respectively. Pulsatile SKF-82958 and cabergoline treatment relieved parkinsonian symptoms, whereas animals continuously treated with SKF-82958 remained akinetic. Pulsatile SKF-82958 induced dyskinesias in two of the three animals tested, whereas cabergoline did not. MPTP induced no significant changes of striatal specific binding of the radioligands used, NR1 mRNA expression and amino acid concentrations. In the putamen, pulsatile SKF-82958 treatment was associated with decreased content of glycine and glutamate, whereas only glycine was decreased in cabergoline-treated monkeys. Cabergoline and continuous administration of SKF-82958 led to lower levels of NR1 mRNA in the caudate in comparison to pulsatile SKF-82958 administration. The development of dyskinesias following a D<sub>1</sub> agonist treatment was associated with an upregulation of <sup>3</sup>H-glutamate [+49%], <sup>3</sup>H-AMPA [+38%], <sup>3</sup>H-CGP39653 [+111%], <sup>3</sup>H-glycine [+26%, nonsignificant] and <sup>3</sup>H-Ro 25-6981 [+33%] specific binding in the striatum in comparison to nondyskinetic MPTP monkeys. Our data suggest that supersensitivity to glutamatergic input in the striatum might play a role in the pathogenesis of dopaminomimetic-induced dyskinesias and further support the therapeutic potential of glutamate antagonists in Parkinson's disease.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name></noRegion><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><name sortKey="Ghribi, Othman" sort="Ghribi, Othman" uniqKey="Ghribi O" first="Othman" last="Ghribi">Othman Ghribi</name><name sortKey="Ghribi, Othman" sort="Ghribi, Othman" uniqKey="Ghribi O" first="Othman" last="Ghribi">Othman Ghribi</name><name sortKey="Ghribi, Othman" sort="Ghribi, Othman" uniqKey="Ghribi O" first="Othman" last="Ghribi">Othman Ghribi</name><name sortKey="Ghribi, Othman" sort="Ghribi, Othman" uniqKey="Ghribi O" first="Othman" last="Ghribi">Othman Ghribi</name><name sortKey="Goulet, Martin" sort="Goulet, Martin" uniqKey="Goulet M" first="Martin" last="Goulet">Martin Goulet</name><name sortKey="Goulet, Martin" sort="Goulet, Martin" uniqKey="Goulet M" first="Martin" last="Goulet">Martin Goulet</name><name sortKey="Grondin, Richard" sort="Grondin, Richard" uniqKey="Grondin R" first="Richard" last="Grondin">Richard Grondin</name><name sortKey="Grondin, Richard" sort="Grondin, Richard" uniqKey="Grondin R" first="Richard" last="Grondin">Richard Grondin</name><name sortKey="Grondin, Richard" sort="Grondin, Richard" uniqKey="Grondin R" first="Richard" last="Grondin">Richard Grondin</name><name sortKey="Grondin, Richard" sort="Grondin, Richard" uniqKey="Grondin R" first="Richard" last="Grondin">Richard Grondin</name><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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