Effect of chronic L-DOPA treatment on 5-HT1A receptors in parkinsonian monkey brain
Identifieur interne : 001534 ( Main/Exploration ); précédent : 001533; suivant : 001535Effect of chronic L-DOPA treatment on 5-HT1A receptors in parkinsonian monkey brain
Auteurs : Golnasim Riahi [Canada] ; Marc Morissette [Canada] ; Daniel Levesque [Canada] ; Claude Rouillard [Canada] ; Pershia Samadi [Canada] ; Martin Parent [Canada] ; Thérèse Di Paolo [Canada]Source :
- Neurochemistry international [ 0197-0186 ] ; 2012.
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Abstract
After chronic use of L-3,4-dihydroxyphenylalanine (L-DOPA), most Parkinson's disease (PD) patients suffer from its side effects, especially motor complications called L-DOPA-induced dyskinesia (LID). 5-HT1A agonists were tested to treat LID but many were reported to worsen parkinsonism. In this study, we evaluated changes in concentration of serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and of 5-HT1A receptors in control monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys, dyskinetic MPTP monkeys treated chronically with L-DOPA, low dyskinetic MPTP monkeys treated with L-DOPA and drugs of various pharmacological activities: Ro 61-8048 (an inhibitor of kynurenine hydroxylase) or docosahexaenoic acid (DHA) and dyskinetic MPTP monkeys treated with L-DOPA + naltrexone (an opioid receptor antagonist). Striatal serotonin concentrations were reduced in MPTP monkeys compared to controls. Higher striatal 5-HIAA/serotonin concentration ratios in L-DOPA-treated monkeys compared to untreated monkeys suggest an intense activity of serotonin axon terminals but this value was similar in dyskinetic and nondyskinetic animals treated with or without adjunct treatment with L-DOPA. As measured by autoradiography with [3H]8-hydroxy-2-(di-n-propyl) aminotetralin (8-OH-DPAT), a decrease of 5-HT1A receptor specific binding was observed in the posterior/dorsal region of the anterior cingulate gyrus and posterior/ventral area of the superior frontal gyrus of MPTP monkeys compared to controls. An increase of 5-HT1A receptor specific binding was observed in the hippocampus of MPTP monkeys treated with L-DOPA regardless to their adjunct treatment. Cortical 5-HT1A receptor specific binding was increased in the L-DOPA-treated MPTP monkeys alone or with DHA or naltrexone and this increase was prevented in low dyskinetic MPTP monkeys treated with L-DOPA and Ro 61-8048. These results highlight the importance of 5-HT1A receptor alterations in treatment of PD with L-DOPA.
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type="wicri:Area/Main/Exploration">001534</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Effect of chronic L-DOPA treatment on 5-HT<sub>1A</sub> receptors in parkinsonian monkey brain</title><author><name sortKey="Riahi, Golnasim" sort="Riahi, Golnasim" uniqKey="Riahi G" first="Golnasim" last="Riahi">Golnasim Riahi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Faculty of Pharmacy, Universite Laval</s1><s2>Quebec City G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec City G1K 7P4</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Axe Endocrinologie et Génomique, Centre de Recherche du CHUQ-CHUL</s1><s2>Quebec City G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec City G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 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Pharmacy, Universite de Montréal</s1><s2>Montreal H3C 3J7</s2><s3>CAN</s3><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Rouillard, Claude" sort="Rouillard, Claude" uniqKey="Rouillard C" first="Claude" last="Rouillard">Claude Rouillard</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Axe Neuroscience, Centre de Recherche du CHUQ-CHUL</s1><s2>Quebec City G1V 4G2</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec City G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Psychiatry and Neuroscience, Université Laval, Faculty of Medicine</s1><s2>Quebec City G1K 7P4</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec City G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Axe Neuroscience, Centre de Recherche du CHUQ-CHUL</s1><s2>Quebec City G1V 4G2</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec City G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Psychiatry and Neuroscience, Université Laval, Faculty of Medicine</s1><s2>Quebec City G1K 7P4</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec City G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Parent, Martin" sort="Parent, Martin" uniqKey="Parent M" first="Martin" last="Parent">Martin Parent</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Psychiatry and Neuroscience, Université Laval, Faculty of Medicine</s1><s2>Quebec City G1K 7P4</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec City G1K 7P4</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Centre de Recherche de l'institut universitaire en sante mentale de Quebec</s1><s2>Quebec City G1J 2G3</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Centre de Recherche de l'institut universitaire en sante mentale de 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>Faculty of Pharmacy, Universite Laval</s1><s2>Quebec City G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec City G1K 7P4</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Axe Endocrinologie et Génomique, Centre de Recherche du CHUQ-CHUL</s1><s2>Quebec City G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec City G1V 4G2</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Neurochemistry international</title><title level="j" type="abbreviated">Neurochem. int.</title><idno type="ISSN">0197-0186</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Neurochemistry international</title><title level="j" type="abbreviated">Neurochem. int.</title><idno type="ISSN">0197-0186</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>5-HT1A Serotonine receptor</term><term>Basal ganglion</term><term>Chronic</term><term>Encephalon</term><term>Levodopa</term><term>Monkey</term><term>Parkinson disease</term><term>Serotonin</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Chronique</term><term>Lévodopa</term><term>Récepteur sérotoninergique 5-HT1A</term><term>Encéphale</term><term>Sérotonine</term><term>Noyau gris central</term><term>Maladie de Parkinson</term><term>Singe</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Singe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">After chronic use of L-3,4-dihydroxyphenylalanine (L-DOPA), most Parkinson's disease (PD) patients suffer from its side effects, especially motor complications called L-DOPA-induced dyskinesia (LID). 5-HT<sub>1A</sub> agonists were tested to treat LID but many were reported to worsen parkinsonism. In this study, we evaluated changes in concentration of serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and of 5-HT<sub>1A</sub> receptors in control monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys, dyskinetic MPTP monkeys treated chronically with L-DOPA, low dyskinetic MPTP monkeys treated with L-DOPA and drugs of various pharmacological activities: Ro 61-8048 (an inhibitor of kynurenine hydroxylase) or docosahexaenoic acid (DHA) and dyskinetic MPTP monkeys treated with <sub>L</sub>-DOPA + naltrexone (an opioid receptor antagonist). Striatal serotonin concentrations were reduced in MPTP monkeys compared to controls. Higher striatal 5-HIAA/serotonin concentration ratios in L-DOPA-treated monkeys compared to untreated monkeys suggest an intense activity of serotonin axon terminals but this value was similar in dyskinetic and nondyskinetic animals treated with or without adjunct treatment with L-DOPA. As measured by autoradiography with [<sup>3</sup>H]8-hydroxy-2-(di-n-propyl) aminotetralin (8-OH-DPAT), a decrease of 5-HT<sub>1A</sub> receptor specific binding was observed in the posterior/dorsal region of the anterior cingulate gyrus and posterior/ventral area of the superior frontal gyrus of MPTP monkeys compared to controls. An increase of 5-HT<sub>1A</sub> receptor specific binding was observed in the hippocampus of MPTP monkeys treated with L-DOPA regardless to their adjunct treatment. Cortical 5-HT<sub>1A</sub> receptor specific binding was increased in the L-DOPA-treated MPTP monkeys alone or with DHA or naltrexone and this increase was prevented in low dyskinetic MPTP monkeys treated with L-DOPA and Ro 61-8048. These results highlight the importance of 5-HT<sub>1A</sub> receptor alterations in treatment of PD with L-DOPA.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Riahi, Golnasim" sort="Riahi, Golnasim" uniqKey="Riahi G" first="Golnasim" last="Riahi">Golnasim Riahi</name></noRegion><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="Levesque, Daniel" sort="Levesque, Daniel" uniqKey="Levesque D" first="Daniel" last="Levesque">Daniel Levesque</name><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name><name sortKey="Parent, Martin" sort="Parent, Martin" uniqKey="Parent M" first="Martin" last="Parent">Martin Parent</name><name sortKey="Parent, Martin" sort="Parent, Martin" uniqKey="Parent M" first="Martin" last="Parent">Martin Parent</name><name sortKey="Riahi, Golnasim" sort="Riahi, Golnasim" uniqKey="Riahi G" first="Golnasim" last="Riahi">Golnasim Riahi</name><name sortKey="Riahi, Golnasim" sort="Riahi, Golnasim" uniqKey="Riahi G" first="Golnasim" last="Riahi">Golnasim Riahi</name><name sortKey="Rouillard, Claude" sort="Rouillard, Claude" uniqKey="Rouillard C" first="Claude" last="Rouillard">Claude Rouillard</name><name sortKey="Rouillard, Claude" sort="Rouillard, Claude" uniqKey="Rouillard C" first="Claude" last="Rouillard">Claude Rouillard</name><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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