Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys : effects on basal ganglia GABAA/ benzodiazepine receptor complex and GABA content
Identifieur interne : 000C69 ( PascalFrancis/Checkpoint ); précédent : 000C68; suivant : 000C70Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys : effects on basal ganglia GABAA/ benzodiazepine receptor complex and GABA content
Auteurs : F. Calon [Canada] ; M. Morissette [Canada] ; M. Goulet [Canada] ; R. Grondin [Canada] ; P. J. Blanchet [Canada] ; P. J. Bedard [Canada] ; T. Di Paolo [Canada]Source :
- Neurochemistry international [ 0197-0186 ] ; 1999.
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Abstract
The effect of various chronic dopaminergic treatments in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys on the brain γ-aminobutyric acid type A (GABAA) /benzodiazepine receptor complex and GABA content was investigated in order to assess the GABAergic involvement in dopaminomimetic-induced dyskinesia. Three MPTP monkeys received for one month pulsatile administrations of the Dl dopamine (DA) receptor agonist SKF 82958 whereas three others received the same dose of SKF 82958 by continuous infusion. A long acting D2 DA receptor agonist, cabergoline, was given to another three animals. Untreated MPTP as well as naive control animals were also included. Pulsatile SKF 82958 relieved parkinsonian symptoms but was also associated with dyskinesia in two of the three animals whereas animals treated continuously with SKF 82958 remained as untreated MPTP monkeys. Chronic cabergoline administration improved motor response with no persistent dyskinesia. MPTP treatment induced a decrease of 3H-flunitrazepam binding in the medial anterior part of caudate-putamen and an increase in the internal segment of globus pallidus (GPi) which was in general unchanged by pulsatile or continuous SKF 82958 administration. Throughout the striatum, binding of 3H-flunitrazepam remained reduced in MPTP monkeys treated with cabergoline but was not significantly lower than untreated MPTP monkeys. Moreover, cabergoline treatment reversed the MPTP-induced increase in 3H-flunitrazepam binding in the GPi. GABA concentrations remained unchanged in the striatum, external segment of globus pallidus and GPi following MPTP denervation. Pulsatile but not continuous SKF 82958 administration decreased putamen GABA content whereas cabergoline treatment decreased caudate GABA. No alteration in GABA levels were observed in the GPe and GPi following the experimental treatments. These results suggest that: (1) D2-like receptor stimulation with cabergoline modulates GABAA receptor density in striatal subregions anatomically related to associative cortical afferent and (2) the absence of dyskinesia in dopaminomimetic-treated monkeys might be associated with the reversal of the MPTP-induced upregulation of the GABAA/benzodiazepine receptor complex in the Gpi.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys : effects on basal ganglia GABA<sub>A</sub>/ benzodiazepine receptor complex and GABA content</title><author><name sortKey="Calon, F" sort="Calon, F" uniqKey="Calon F" first="F." last="Calon">F. Calon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Morissette, M" sort="Morissette, M" uniqKey="Morissette M" first="M." last="Morissette">M. Morissette</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Goulet, M" sort="Goulet, M" uniqKey="Goulet M" first="M." last="Goulet">M. Goulet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Grondin, R" sort="Grondin, R" uniqKey="Grondin R" first="R." last="Grondin">R. Grondin</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Quebec, G1V 4G2</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec, 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>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Blanchet, P J" sort="Blanchet, P J" uniqKey="Blanchet P" first="P. J." last="Blanchet">P. J. Blanchet</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Quebec, G1V 4G2</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec, 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>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Bedard, P J" sort="Bedard, P J" uniqKey="Bedard P" first="P. J." last="Bedard">P. J. Bedard</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Quebec, G1V 4G2</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec, 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>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, T" sort="Di Paolo, T" uniqKey="Di Paolo T" first="T." last="Di Paolo">T. Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">99-0333352</idno><date when="1999">1999</date><idno type="stanalyst">PASCAL 99-0333352 INIST</idno><idno type="RBID">Pascal:99-0333352</idno><idno type="wicri:Area/PascalFrancis/Corpus">000D58</idno><idno type="wicri:Area/PascalFrancis/Curation">001165</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000C69</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000C69</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys : effects on basal ganglia GABA<sub>A</sub>/ benzodiazepine receptor complex and GABA content</title><author><name sortKey="Calon, F" sort="Calon, F" uniqKey="Calon F" first="F." last="Calon">F. Calon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Morissette, M" sort="Morissette, M" uniqKey="Morissette M" first="M." last="Morissette">M. Morissette</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Goulet, M" sort="Goulet, M" uniqKey="Goulet M" first="M." last="Goulet">M. Goulet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Grondin, R" sort="Grondin, R" uniqKey="Grondin R" first="R." last="Grondin">R. Grondin</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Quebec, G1V 4G2</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec, 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>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Blanchet, P J" sort="Blanchet, P J" uniqKey="Blanchet P" first="P. J." last="Blanchet">P. J. Blanchet</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Quebec, G1V 4G2</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec, 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>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Bedard, P J" sort="Bedard, P J" uniqKey="Bedard P" first="P. J." last="Bedard">P. J. Bedard</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Quebec, G1V 4G2</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec, 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>Québec, G1K 7P4</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, T" sort="Di Paolo, T" uniqKey="Di Paolo T" first="T." last="Di Paolo">T. Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, G1K 7P4</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="1999">1999</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>Agonist</term><term>Animal</term><term>Basal ganglion</term><term>Benzodiazepine receptor</term><term>Chronic</term><term>D1 Dopamine receptor</term><term>D2 Dopamine receptor</term><term>Dyskinesia</term><term>Experimental disease</term><term>GABA</term><term>Gabaergic receptor A</term><term>Monkey</term><term>Neurotoxin</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Chronique</term><term>Neurotoxine</term><term>Noyau gris central</term><term>Récepteur benzodiazépinique</term><term>Récepteur gabaergique A</term><term>GABA</term><term>Dyskinésie</term><term>Agoniste</term><term>Parkinson maladie</term><term>Récepteur dopaminergique D1</term><term>Récepteur dopaminergique D2</term><term>Pathologie expérimentale</term><term>Animal</term><term>Singe</term><term>MPTP</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 effect of various chronic dopaminergic treatments in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys on the brain γ-aminobutyric acid type A (GABA<sub>A</sub>) /benzodiazepine receptor complex and GABA content was investigated in order to assess the GABAergic involvement in dopaminomimetic-induced dyskinesia. Three MPTP monkeys received for one month pulsatile administrations of the Dl dopamine (DA) receptor agonist SKF 82958 whereas three others received the same dose of SKF 82958 by continuous infusion. A long acting D2 DA receptor agonist, cabergoline, was given to another three animals. Untreated MPTP as well as naive control animals were also included. Pulsatile SKF 82958 relieved parkinsonian symptoms but was also associated with dyskinesia in two of the three animals whereas animals treated continuously with SKF 82958 remained as untreated MPTP monkeys. Chronic cabergoline administration improved motor response with no persistent dyskinesia. MPTP treatment induced a decrease of <sup>3</sup>H-flunitrazepam binding in the medial anterior part of caudate-putamen and an increase in the internal segment of globus pallidus (GPi) which was in general unchanged by pulsatile or continuous SKF 82958 administration. Throughout the striatum, binding of <sup>3</sup>H-flunitrazepam remained reduced in MPTP monkeys treated with cabergoline but was not significantly lower than untreated MPTP monkeys. Moreover, cabergoline treatment reversed the MPTP-induced increase in <sup>3</sup>H-flunitrazepam binding in the GPi. GABA concentrations remained unchanged in the striatum, external segment of globus pallidus and GPi following MPTP denervation. Pulsatile but not continuous SKF 82958 administration decreased putamen GABA content whereas cabergoline treatment decreased caudate GABA. No alteration in GABA levels were observed in the GPe and GPi following the experimental treatments. These results suggest that: (1) D2-like receptor stimulation with cabergoline modulates GABA<sub>A</sub> receptor density in striatal subregions anatomically related to associative cortical afferent and (2) the absence of dyskinesia in dopaminomimetic-treated monkeys might be associated with the reversal of the MPTP-induced upregulation of the GABA<sub>A</sub>/benzodiazepine receptor complex in the Gpi.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0197-0186</s0></fA01><fA02 i1="01"><s0>NEUIDS</s0></fA02><fA03 i2="1"><s0>Neurochem. int.</s0></fA03><fA05><s2>35</s2></fA05><fA06><s2>1</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys : effects on basal ganglia GABA<sub>A</sub>/ benzodiazepine receptor complex and GABA content</s1></fA08><fA11 i1="01" i2="1"><s1>CALON (F.)</s1></fA11><fA11 i1="02" i2="1"><s1>MORISSETTE (M.)</s1></fA11><fA11 i1="03" i2="1"><s1>GOULET (M.)</s1></fA11><fA11 i1="04" i2="1"><s1>GRONDIN (R.)</s1></fA11><fA11 i1="05" i2="1"><s1>BLANCHET (P. J.)</s1></fA11><fA11 i1="06" i2="1"><s1>BEDARD (P. J.)</s1></fA11><fA11 i1="07" i2="1"><s1>DI PAOLO (T.)</s1></fA11><fA14 i1="01"><s1>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Québec, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></fA14><fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></fA14><fA14 i1="03"><s1>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL</s1><s2>Quebec, G1V 4G2</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec, G1K 7P4</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></fA14><fA20><s1>81-91</s1></fA20><fA21><s1>1999</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>18809</s2><s5>354000085470520090</s5></fA43><fA44><s0>0000</s0><s1>© 1999 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>1 p.1/2</s0></fA45><fA47 i1="01" i2="1"><s0>99-0333352</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Neurochemistry international</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>The effect of various chronic dopaminergic treatments in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys on the brain γ-aminobutyric acid type A (GABA<sub>A</sub>) /benzodiazepine receptor complex and GABA content was investigated in order to assess the GABAergic involvement in dopaminomimetic-induced dyskinesia. Three MPTP monkeys received for one month pulsatile administrations of the Dl dopamine (DA) receptor agonist SKF 82958 whereas three others received the same dose of SKF 82958 by continuous infusion. A long acting D2 DA receptor agonist, cabergoline, was given to another three animals. Untreated MPTP as well as naive control animals were also included. Pulsatile SKF 82958 relieved parkinsonian symptoms but was also associated with dyskinesia in two of the three animals whereas animals treated continuously with SKF 82958 remained as untreated MPTP monkeys. Chronic cabergoline administration improved motor response with no persistent dyskinesia. MPTP treatment induced a decrease of <sup>3</sup>H-flunitrazepam binding in the medial anterior part of caudate-putamen and an increase in the internal segment of globus pallidus (GPi) which was in general unchanged by pulsatile or continuous SKF 82958 administration. Throughout the striatum, binding of <sup>3</sup>H-flunitrazepam remained reduced in MPTP monkeys treated with cabergoline but was not significantly lower than untreated MPTP monkeys. Moreover, cabergoline treatment reversed the MPTP-induced increase in <sup>3</sup>H-flunitrazepam binding in the GPi. GABA concentrations remained unchanged in the striatum, external segment of globus pallidus and GPi following MPTP denervation. Pulsatile but not continuous SKF 82958 administration decreased putamen GABA content whereas cabergoline treatment decreased caudate GABA. No alteration in GABA levels were observed in the GPe and GPi following the experimental treatments. These results suggest that: (1) D2-like receptor stimulation with cabergoline modulates GABA<sub>A</sub> receptor density in striatal subregions anatomically related to associative cortical afferent and (2) the absence of dyskinesia in dopaminomimetic-treated monkeys might be associated with the reversal of the MPTP-induced upregulation of the GABA<sub>A</sub>/benzodiazepine receptor complex in the Gpi.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Chronique</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Chronic</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Crónico</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Neurotoxine</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Neurotoxin</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Neurotoxina</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Noyau gris central</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Basal ganglion</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Núcleo basal</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Récepteur benzodiazépinique</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Benzodiazepine receptor</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Receptor benzodiazepínico</s0><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Récepteur gabaergique A</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Gabaergic receptor A</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Receptor gabaminérgico A</s0><s5>05</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>GABA</s0><s2>NK</s2><s5>06</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>GABA</s0><s2>NK</s2><s5>06</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>GABA</s0><s2>NK</s2><s5>06</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Dyskinésie</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Dyskinesia</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Disquinesia</s0><s5>07</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Agoniste</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Agonist</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Agonista</s0><s5>08</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Parkinson maladie</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Parkinson disease</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s5>09</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Récepteur dopaminergique D1</s0><s5>10</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>D1 Dopamine receptor</s0><s5>10</s5><s6>«D1» Dopamine receptor</s6></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Receptor dopaminérgico D1</s0><s5>10</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Récepteur dopaminergique D2</s0><s5>11</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>D2 Dopamine receptor</s0><s5>11</s5><s6>«D2» Dopamine receptor</s6></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Receptor dopaminérgico D2</s0><s5>11</s5></fC03><fC03 i1="12" i2="X" l="FRE"><s0>Pathologie expérimentale</s0><s5>13</s5></fC03><fC03 i1="12" i2="X" l="ENG"><s0>Experimental disease</s0><s5>13</s5></fC03><fC03 i1="12" i2="X" l="SPA"><s0>Patología experimental</s0><s5>13</s5></fC03><fC03 i1="13" i2="X" l="FRE"><s0>Animal</s0><s5>14</s5></fC03><fC03 i1="13" i2="X" l="ENG"><s0>Animal</s0><s5>14</s5></fC03><fC03 i1="13" i2="X" l="SPA"><s0>Animal</s0><s5>14</s5></fC03><fC03 i1="14" i2="X" l="FRE"><s0>Singe</s0><s5>54</s5></fC03><fC03 i1="14" i2="X" l="ENG"><s0>Monkey</s0><s5>54</s5></fC03><fC03 i1="14" i2="X" l="SPA"><s0>Mono</s0><s5>54</s5></fC03><fC03 i1="15" i2="X" l="FRE"><s0>MPTP</s0><s4>INC</s4><s5>81</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Encéphale</s0><s5>26</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Brain (vertebrata)</s0><s5>26</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Encéfalo</s0><s5>26</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Système nerveux central</s0><s5>27</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Central nervous system</s0><s5>27</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Sistema nervioso central</s0><s5>27</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Système nerveux pathologie</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>38</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Système nerveux central pathologie</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>39</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Encéphale pathologie</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>40</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Extrapyramidal syndrome</s0><s5>41</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>41</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>41</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>42</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>42</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>42</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Primates</s0><s2>NS</s2></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Primates</s0><s2>NS</s2></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Primates</s0><s2>NS</s2></fC07><fC07 i1="09" i2="X" l="FRE"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="09" i2="X" l="ENG"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="09" i2="X" l="SPA"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="10" i2="X" l="FRE"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="10" i2="X" l="ENG"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="10" i2="X" l="SPA"><s0>Vertebrata</s0><s2>NS</s2></fC07><fN21><s1>207</s1></fN21></pA></standard></inist><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Calon, F" sort="Calon, F" uniqKey="Calon F" first="F." last="Calon">F. Calon</name></noRegion><name sortKey="Bedard, P J" sort="Bedard, P J" uniqKey="Bedard P" first="P. J." last="Bedard">P. J. Bedard</name><name sortKey="Bedard, P J" sort="Bedard, P J" uniqKey="Bedard P" first="P. J." last="Bedard">P. J. Bedard</name><name sortKey="Blanchet, P J" sort="Blanchet, P J" uniqKey="Blanchet P" first="P. J." last="Blanchet">P. J. Blanchet</name><name sortKey="Blanchet, P J" sort="Blanchet, P J" uniqKey="Blanchet P" first="P. J." last="Blanchet">P. J. Blanchet</name><name sortKey="Calon, F" sort="Calon, F" uniqKey="Calon F" first="F." last="Calon">F. Calon</name><name sortKey="Di Paolo, T" sort="Di Paolo, T" uniqKey="Di Paolo T" first="T." last="Di Paolo">T. Di Paolo</name><name sortKey="Di Paolo, T" sort="Di Paolo, T" uniqKey="Di Paolo T" first="T." last="Di Paolo">T. Di Paolo</name><name sortKey="Goulet, M" sort="Goulet, M" uniqKey="Goulet M" first="M." last="Goulet">M. Goulet</name><name sortKey="Goulet, M" sort="Goulet, M" uniqKey="Goulet M" first="M." last="Goulet">M. Goulet</name><name sortKey="Grondin, R" sort="Grondin, R" uniqKey="Grondin R" first="R." last="Grondin">R. Grondin</name><name sortKey="Grondin, R" sort="Grondin, R" uniqKey="Grondin R" first="R." last="Grondin">R. Grondin</name><name sortKey="Grondin, R" sort="Grondin, R" uniqKey="Grondin R" first="R." last="Grondin">R. Grondin</name><name sortKey="Grondin, R" sort="Grondin, R" uniqKey="Grondin R" first="R." last="Grondin">R. Grondin</name><name sortKey="Morissette, M" sort="Morissette, M" uniqKey="Morissette M" first="M." last="Morissette">M. Morissette</name><name sortKey="Morissette, M" sort="Morissette, M" uniqKey="Morissette M" first="M." last="Morissette">M. Morissette</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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