La maladie de Parkinson au Canada (serveur d'exploration)

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Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys : effects on basal ganglia GABAA/ benzodiazepine receptor complex and GABA content

Identifieur interne : 003E22 ( Main/Merge ); précédent : 003E21; suivant : 003E23

Chronic 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 :

RBID : Pascal:99-0333352

Descripteurs français

English descriptors

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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Pascal:99-0333352

Le document en format XML

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</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>
<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>

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