Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABAA/benzodiazepine receptor complex and GABA content
Identifieur interne : 001627 ( Istex/Corpus ); précédent : 001626; suivant : 001628Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABAA/benzodiazepine receptor complex and GABA content
Auteurs : Frédéric Calon ; Marc Morissette ; Martin Goulet ; Richard Grondin ; Pierre J. Blanchet ; Paul J. Bédard ; Thérèse Di PaoloSource :
- Neurochemistry International [ 0197-0186 ] ; 1999.
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 D1 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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DOI: 10.1016/S0197-0186(99)00064-9
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Blanchet</name><affiliation><mods:affiliation>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J" last="Bédard">Paul J. Bédard</name><affiliation><mods:affiliation>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></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><mods:affiliation>E-mail: therese.dipaolo@crchul.ulaval.ca</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:E53B627CD5410880AC565F2E90E0D394A66D7DCD</idno><date when="1999" year="1999">1999</date><idno type="doi">10.1016/S0197-0186(99)00064-9</idno><idno type="url">https://api-v5.istex.fr/document/E53B627CD5410880AC565F2E90E0D394A66D7DCD/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001627</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001627</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABAA/benzodiazepine receptor complex and GABA content</title><author><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><affiliation><mods:affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></affiliation></author><author><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name><affiliation><mods:affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></affiliation></author><author><name sortKey="Goulet, Martin" sort="Goulet, Martin" uniqKey="Goulet M" first="Martin" last="Goulet">Martin Goulet</name><affiliation><mods:affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></affiliation></author><author><name sortKey="Grondin, Richard" sort="Grondin, Richard" uniqKey="Grondin R" first="Richard" last="Grondin">Richard Grondin</name><affiliation><mods:affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></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><mods:affiliation>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J" last="Bédard">Paul J. Bédard</name><affiliation><mods:affiliation>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></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><mods:affiliation>E-mail: therese.dipaolo@crchul.ulaval.ca</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Neurochemistry International</title><title level="j" type="abbrev">NCI</title><idno type="ISSN">0197-0186</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">35</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="81">81</biblScope><biblScope unit="page" to="91">91</biblScope></imprint><idno type="ISSN">0197-0186</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0197-0186</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></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 (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 D1 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.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>Frédéric Calon</name><affiliations><json:string>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</json:string></affiliations></json:item><json:item><name>Marc Morissette</name><affiliations><json:string>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</json:string></affiliations></json:item><json:item><name>Martin Goulet</name><affiliations><json:string>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</json:string></affiliations></json:item><json:item><name>Richard Grondin</name><affiliations><json:string>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</json:string></affiliations></json:item><json:item><name>Pierre J Blanchet</name><affiliations><json:string>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</json:string></affiliations></json:item><json:item><name>Paul J Bédard</name><affiliations><json:string>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</json:string></affiliations></json:item><json:item><name>Thérèse Di Paolo</name><affiliations><json:string>E-mail: therese.dipaolo@crchul.ulaval.ca</json:string><json:string>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson’s disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Globus Pallidus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Dyskinesia</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Dopamine agonist</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>GABA</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MPTP</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Flunitrazepam</value></json:item></subject><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><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 D1 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.</abstract><qualityIndicators><score>8</score><pdfWordCount>6508</pdfWordCount><pdfCharCount>42285</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>11</pdfPageCount><pdfPageSize>595 x 794 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>307</abstractWordCount><abstractCharCount>2257</abstractCharCount><keywordCount>7</keywordCount></qualityIndicators><title>Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABAA/benzodiazepine receptor complex and GABA content</title><pii><json:string>S0197-0186(99)00064-9</json:string></pii><genre><json:string>research-article</json:string></genre><serie><title>Dopamine Agonist in Early Parkinson’s Disease Beyond the Decade of the Brain</title><language><json:string>unknown</json:string></language><volume>vol. 2</volume><pages><first>101</first><last>115</last></pages></serie><host><title>Neurochemistry International</title><language><json:string>unknown</json:string></language><publicationDate>1999</publicationDate><issn><json:string>0197-0186</json:string></issn><pii><json:string>S0197-0186(00)X0050-2</json:string></pii><volume>35</volume><issue>1</issue><pages><first>81</first><last>91</last></pages><genre><json:string>journal</json:string></genre></host><categories><wos><json:string>science</json:string><json:string>neurosciences</json:string><json:string>biochemistry & molecular biology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>neurology & neurosurgery</json:string></scienceMetrix><inist><json:string>sciences appliquees, technologies et medecines</json:string><json:string>sciences biologiques et medicales</json:string><json:string>sciences medicales</json:string><json:string>neurologie</json:string></inist></categories><publicationDate>1999</publicationDate><copyrightDate>1999</copyrightDate><doi><json:string>10.1016/S0197-0186(99)00064-9</json:string></doi><id>E53B627CD5410880AC565F2E90E0D394A66D7DCD</id><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api-v5.istex.fr/document/E53B627CD5410880AC565F2E90E0D394A66D7DCD/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api-v5.istex.fr/document/E53B627CD5410880AC565F2E90E0D394A66D7DCD/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api-v5.istex.fr/document/E53B627CD5410880AC565F2E90E0D394A66D7DCD/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABAA/benzodiazepine receptor complex and GABA content</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>©1999 Elsevier Science Ltd</p></availability><date>1999</date></publicationStmt><notesStmt><note type="content">Fig. 1: Autoradiograms of 3H-FNZ binding to brain slices (including caudate, putamen, GPe, and GPi) of a drug naive monkey (control), an untreated MPTP monkey (MPTP+saline), a MPTP monkey treated chronically with injections of SKF 82958 (SKF pulse), a MPTP monkey treated with SKF 82958 administered through an osmotic mini-pump (SKF pump) and a MPTP monkey treated with cabergoline. Note that the animal treated with injections of SKF 82958 developed dyskinesia.</note><note type="content">Fig. 2: Effect of chronic treatment of MPTP monkeys with the D1 agonist SKF 82958 by injections (PULSE) or through osmotic mini-pumps (PUMP) or with cabergoline (CAB) as compared to saline-treated MPTP and control monkeys on the caudate nucleus 3H-FNZ specific binding to GABAA/benzodiazepine receptor complex. Values were expressed as the mean±SEM of three animals per group. ∗ P<0.05, ∗∗ P<0.01 vs control; ‡ P<0.05 vs PULSE; § P<0.05 vs PUMP, using an ANOVA followed by post-hoc pairwise comparisons with Fisher’s probability of least significant difference test (PLSD).</note><note type="content">Fig. 3: Effect of chronic treatment of MPTP monkeys with the D1 agonist SKF 82958 by injections (PULSE) or through osmotic mini-pumps (PUMP) or with cabergoline (CAB) as compared to saline-treated MPTP and control monkeys on the putamen 3H-FNZ specific binding to GABAA/benzodiazepine receptor complex. Values were expressed as the mean±SEM of three animals per group. ∗ P<0.05, ∗∗ P<0.01 vs control; § P<0.05 vs PUMP, using an ANOVA followed by post-hoc pairwise comparisons with Fisher’s probability of least significant difference test (PLSD).</note><note type="content">Fig. 4: Effect of chronic treatment of MPTP monkeys with the D1 agonist SKF 82958 (SKF) by injections (PULSE) or through osmotic mini-pumps (PUMP) or with cabergoline (CAB) as compared to saline-treated MPTP and control monkeys on the external and internal segment of the globus pallidus 3H-FNZ specific binding to GABAA/benzodiazepine receptor complex. Values were expressed as the mean±SEM of 3 animals per group. ∗ P<0.05 vs control; † P<0.05 vs MPTP+saline, using an ANOVA followed by post-hoc pairwise comparisons with Fisher’s probability of least significant difference test (PLSD).</note><note type="content">Fig. 5: Comparison of 3H-FNZ binding to GABAA/benzodiazepine receptor complex in GPi between dyskinetic (n=2) compared to nondyskinetic (n=4) MPTP monkeys which showed good antiparkinsonian response following treatment with injections of SKF 82958 or cabergoline. Values were expressed as the mean±SEM. ∗ P<0.05 vs dyskinetic animals, using an ANOVA followed by post-hoc pairwise comparisons with Fisher’s probability of least significant difference test (PLSD).</note><note type="content">Table 1: Effect on GABA content of chronic treatment of MPTP monkeys with the D1 agonist SKF 82958 by injections (PULSE) or through osmotic mini-pumps (PUMP) or with cabergoline (CAB) as compared to saline-treated MPTP and control monkeys in basal gangliaa</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABAA/benzodiazepine receptor complex and GABA content</title><author xml:id="author-0000"><persName><forename type="first">Frédéric</forename><surname>Calon</surname></persName><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Marc</forename><surname>Morissette</surname></persName><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Martin</forename><surname>Goulet</surname></persName><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Richard</forename><surname>Grondin</surname></persName><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Pierre J</forename><surname>Blanchet</surname></persName><affiliation>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Paul J</forename><surname>Bédard</surname></persName><affiliation>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Thérèse</forename><surname>Di Paolo</surname></persName><email>therese.dipaolo@crchul.ulaval.ca</email><note type="correspondence"><p>Corresponding author. Tel.: +1-418-654-2296; fax: +1-418-654-2761</p></note><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation></author><idno type="istex">E53B627CD5410880AC565F2E90E0D394A66D7DCD</idno><idno type="DOI">10.1016/S0197-0186(99)00064-9</idno><idno type="PII">S0197-0186(99)00064-9</idno></analytic><monogr><title level="j">Neurochemistry International</title><title level="j" type="abbrev">NCI</title><idno type="pISSN">0197-0186</idno><idno type="PII">S0197-0186(00)X0050-2</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999"></date><biblScope unit="volume">35</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="81">81</biblScope><biblScope unit="page" to="91">91</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1999</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>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 D1 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.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson’s disease</term></item><item><term>Globus Pallidus</term></item><item><term>Dyskinesia</term></item><item><term>Dopamine agonist</term></item><item><term>GABA</term></item><item><term>MPTP</term></item><item><term>Flunitrazepam</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1999">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api-v5.istex.fr/document/E53B627CD5410880AC565F2E90E0D394A66D7DCD/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity><istex:entity SYSTEM="gr5" NDATA="IMAGE" name="gr5"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>NCI</jid><aid>825</aid><ce:pii>S0197-0186(99)00064-9</ce:pii><ce:doi>10.1016/S0197-0186(99)00064-9</ce:doi><ce:copyright type="full-transfer" year="1999">Elsevier Science Ltd</ce:copyright></item-info><head><ce:title>Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABA<ce:inf>A</ce:inf>/benzodiazepine receptor complex and GABA content</ce:title><ce:author-group><ce:author><ce:given-name>Frédéric</ce:given-name><ce:surname>Calon</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Marc</ce:given-name><ce:surname>Morissette</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Martin</ce:given-name><ce:surname>Goulet</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Richard</ce:given-name><ce:surname>Grondin</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Pierre J</ce:given-name><ce:surname>Blanchet</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Paul J</ce:given-name><ce:surname>Bédard</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Thérèse</ce:given-name><ce:surname>Di Paolo</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref><ce:e-address>therese.dipaolo@crchul.ulaval.ca</ce:e-address></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Faculty of Pharmacy, Laval University, Québec, Canada, G1K 7P4</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</ce:textfn></ce:affiliation><ce:affiliation id="AFF4"><ce:label>d</ce:label><ce:textfn>Department of Medicine, Faculty of Medicine, Laval University, Québec, Canada, G1K 7P4</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel.: +1-418-654-2296; fax: +1-418-654-2761</ce:text></ce:correspondence></ce:author-group><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>The effect of various chronic dopaminergic treatments in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys on the brain <ce:italic>γ</ce:italic>-aminobutyric acid type A (GABA<ce:inf>A</ce:inf>) /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 D1 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 <ce:sup>3</ce: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 <ce:sup>3</ce: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 <ce:sup>3</ce: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<ce:inf>A</ce:inf> 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<ce:inf>A</ce:inf>/benzodiazepine receptor complex in the Gpi.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Parkinson’s disease</ce:text></ce:keyword><ce:keyword><ce:text>Globus Pallidus</ce:text></ce:keyword><ce:keyword><ce:text>Dyskinesia</ce:text></ce:keyword><ce:keyword><ce:text>Dopamine agonist</ce:text></ce:keyword><ce:keyword><ce:text>GABA</ce:text></ce:keyword><ce:keyword><ce:text>MPTP</ce:text></ce:keyword><ce:keyword><ce:text>Flunitrazepam</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABAA/benzodiazepine receptor complex and GABA content</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABA</title></titleInfo><name type="personal"><namePart type="given">Frédéric</namePart><namePart type="family">Calon</namePart><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marc</namePart><namePart type="family">Morissette</namePart><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martin</namePart><namePart type="family">Goulet</namePart><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Richard</namePart><namePart type="family">Grondin</namePart><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Pierre J</namePart><namePart type="family">Blanchet</namePart><affiliation>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Paul J</namePart><namePart type="family">Bédard</namePart><affiliation>Unité de Recherche en Neuroscience, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thérèse</namePart><namePart type="family">Di Paolo</namePart><affiliation>E-mail: therese.dipaolo@crchul.ulaval.ca</affiliation><affiliation>Centre de Recherches en Endocrinologie Moléculaire, Le Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, Canada, G1V 4G2</affiliation><description>Corresponding author. Tel.: +1-418-654-2296; fax: +1-418-654-2761</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1999</dateIssued><copyrightDate encoding="w3cdtf">1999</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract 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 (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 D1 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.</abstract><note type="content">Fig. 1: Autoradiograms of 3H-FNZ binding to brain slices (including caudate, putamen, GPe, and GPi) of a drug naive monkey (control), an untreated MPTP monkey (MPTP+saline), a MPTP monkey treated chronically with injections of SKF 82958 (SKF pulse), a MPTP monkey treated with SKF 82958 administered through an osmotic mini-pump (SKF pump) and a MPTP monkey treated with cabergoline. Note that the animal treated with injections of SKF 82958 developed dyskinesia.</note><note type="content">Fig. 2: Effect of chronic treatment of MPTP monkeys with the D1 agonist SKF 82958 by injections (PULSE) or through osmotic mini-pumps (PUMP) or with cabergoline (CAB) as compared to saline-treated MPTP and control monkeys on the caudate nucleus 3H-FNZ specific binding to GABAA/benzodiazepine receptor complex. Values were expressed as the mean±SEM of three animals per group. ∗ P<0.05, ∗∗ P<0.01 vs control; ‡ P<0.05 vs PULSE; § P<0.05 vs PUMP, using an ANOVA followed by post-hoc pairwise comparisons with Fisher’s probability of least significant difference test (PLSD).</note><note type="content">Fig. 3: Effect of chronic treatment of MPTP monkeys with the D1 agonist SKF 82958 by injections (PULSE) or through osmotic mini-pumps (PUMP) or with cabergoline (CAB) as compared to saline-treated MPTP and control monkeys on the putamen 3H-FNZ specific binding to GABAA/benzodiazepine receptor complex. Values were expressed as the mean±SEM of three animals per group. ∗ P<0.05, ∗∗ P<0.01 vs control; § P<0.05 vs PUMP, using an ANOVA followed by post-hoc pairwise comparisons with Fisher’s probability of least significant difference test (PLSD).</note><note type="content">Fig. 4: Effect of chronic treatment of MPTP monkeys with the D1 agonist SKF 82958 (SKF) by injections (PULSE) or through osmotic mini-pumps (PUMP) or with cabergoline (CAB) as compared to saline-treated MPTP and control monkeys on the external and internal segment of the globus pallidus 3H-FNZ specific binding to GABAA/benzodiazepine receptor complex. Values were expressed as the mean±SEM of 3 animals per group. ∗ P<0.05 vs control; † P<0.05 vs MPTP+saline, using an ANOVA followed by post-hoc pairwise comparisons with Fisher’s probability of least significant difference test (PLSD).</note><note type="content">Fig. 5: Comparison of 3H-FNZ binding to GABAA/benzodiazepine receptor complex in GPi between dyskinetic (n=2) compared to nondyskinetic (n=4) MPTP monkeys which showed good antiparkinsonian response following treatment with injections of SKF 82958 or cabergoline. Values were expressed as the mean±SEM. ∗ P<0.05 vs dyskinetic animals, using an ANOVA followed by post-hoc pairwise comparisons with Fisher’s probability of least significant difference test (PLSD).</note><note type="content">Table 1: Effect on GABA content of chronic treatment of MPTP monkeys with the D1 agonist SKF 82958 by injections (PULSE) or through osmotic mini-pumps (PUMP) or with cabergoline (CAB) as compared to saline-treated MPTP and control monkeys in basal gangliaa</note><subject><genre>Keywords</genre><topic>Parkinson’s disease</topic><topic>Globus Pallidus</topic><topic>Dyskinesia</topic><topic>Dopamine agonist</topic><topic>GABA</topic><topic>MPTP</topic><topic>Flunitrazepam</topic></subject><relatedItem type="host"><titleInfo><title>Neurochemistry International</title></titleInfo><titleInfo type="abbreviated"><title>NCI</title></titleInfo><genre type="journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">199907</dateIssued></originInfo><identifier type="ISSN">0197-0186</identifier><identifier type="PII">S0197-0186(00)X0050-2</identifier><part><date>199907</date><detail type="volume"><number>35</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue pages"><start>1</start><end>92</end></extent><extent unit="pages"><start>81</start><end>91</end></extent></part></relatedItem><identifier type="istex">E53B627CD5410880AC565F2E90E0D394A66D7DCD</identifier><identifier type="DOI">10.1016/S0197-0186(99)00064-9</identifier><identifier type="PII">S0197-0186(99)00064-9</identifier><accessCondition type="use and reproduction" contentType="copyright">©1999 Elsevier Science Ltd</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Elsevier Science Ltd, ©1999</recordOrigin></recordInfo></mods></metadata></istex></record>Pour manipuler ce document sous Unix (Dilib)
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