125I-CGP 64213 Binding to GABAB Receptors in the Brain of Monkeys: Effect of MPTP and Dopaminomimetic Treatments
Identifieur interne : 003545 ( Main/Exploration ); précédent : 003544; suivant : 003546125I-CGP 64213 Binding to GABAB Receptors in the Brain of Monkeys: Effect of MPTP and Dopaminomimetic Treatments
Auteurs : Frédéric Calon ; Marc Morissette ; Martin Goulet ; Richard Grondin ; Pierre J. Blanchet ; Paul J. Bédard ; Thérèse Di PaoloSource :
- Experimental Neurology [ 0014-4886 ] ; 2000.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Antiparkinson Agents (pharmacology), Autoradiography, Basal Ganglia (drug effects), Basal Ganglia (metabolism), Basal Ganglia (pathology), Benzazepines (pharmacology), Benzoates (metabolism), Binding Sites, Brain (drug effects), Brain (metabolism), Brain (pathology), Corpus Striatum (drug effects), Dopamine Agonists (pharmacology), Drug Administration Schedule, Dyskinesia, Drug-Induced (metabolism), Ergolines (pharmacology), Female, GABA, GABA Antagonists (metabolism), GABA-B Receptor Antagonists, Injections, Subcutaneous, Iodine Radioisotopes, Macaca fascicularis, Organophosphorus Compounds (metabolism), Parkinson, Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (drug therapy), Parkinson Disease, Secondary (metabolism), Receptors, GABA-B (metabolism), Substantia Nigra (drug effects), Substantia Nigra (pathology), Thalamus (drug effects), Thalamus (metabolism), Thalamus (pathology), autoradiography, basal ganglia, dopamine agonist, dyskinesia.
- MESH :
- chemical , metabolism : Benzoates, GABA Antagonists, Organophosphorus Compounds, Receptors, GABA-B.
- chemical , pharmacology : Antiparkinson Agents, Benzazepines, Dopamine Agonists, Ergolines.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, GABA-B Receptor Antagonists, Iodine Radioisotopes.
- chemically induced : Parkinson Disease, Secondary.
- drug effects : Basal Ganglia, Brain, Corpus Striatum, Substantia Nigra, Thalamus.
- drug therapy : Parkinson Disease, Secondary.
- metabolism : Basal Ganglia, Brain, Dyskinesia, Drug-Induced, Parkinson Disease, Secondary, Thalamus.
- pathology : Basal Ganglia, Brain, Substantia Nigra, Thalamus.
- Animals, Autoradiography, Binding Sites, Drug Administration Schedule, Female, Injections, Subcutaneous, Macaca fascicularis.
Abstract
Much evidence indicates that abnormal GABA neurotransmission may be implicated in the pathophysiology of Parkinson's disease (PD) and dopaminomimetic-induced dyskinesias (DID). In this study, autoradiography using 125I-CGP 64213 was performed to investigate GABAB receptor density in the brain of control monkeys as well as monkeys with MPTP-induced nigrostriatal depletion. Three MPTP monkeys received pulsatile administrations of the D1 dopamine (DA) receptor agonist (SKF 82958) whereas a long-acting D2 DA receptor agonist (cabergoline) was given to another three animals. SKF 82958 treatment relieved parkinsonian symptoms but two of three animals developed DID. Cabergoline induced a comparable motor benefit effect without persistent DID. 125I-CGP 64213 binding to GABAB receptors was heterogeneous throughout the brain with the highest levels in the medial habenula of the thalamus. MPTP induced a decrease (−40%) of 125I-CGP 64213 binding to GABAB receptors in the substantia nigra pars compacta (SNpc) and an increase (+29%) in the internal segment of the globus pallidus (GPi). This increase in the GPi was not affected by SKF 82958 but partly reversed by cabergoline. No change was seen in the striatum, the thalamus, the external segment of the globus pallidus, and the substantia nigra pars reticulata following MPTP and dopaminomimetic treatments. The changes of GABAB receptors observed in the SNpc and in the GPi suggest that alteration of GABAB receptors may play a role in the pathophysiology of PD and DID.
Url:
DOI: 10.1006/exnr.2000.7366
Affiliations:
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Blanchet</name><affiliation><wicri:noCountry code="subField">4G2</wicri:noCountry></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><wicri:noCountry code="subField">4G2</wicri:noCountry></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:noCountry code="subField">4G2</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j">Experimental Neurology</title><title level="j" type="abbrev">YEXNR</title><idno type="ISSN">0014-4886</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000">2000</date><biblScope unit="volume">163</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="191">191</biblScope><biblScope unit="page" to="199">199</biblScope></imprint><idno type="ISSN">0014-4886</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0014-4886</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Animals</term><term>Antiparkinson Agents (pharmacology)</term><term>Autoradiography</term><term>Basal Ganglia (drug effects)</term><term>Basal Ganglia (metabolism)</term><term>Basal Ganglia (pathology)</term><term>Benzazepines (pharmacology)</term><term>Benzoates (metabolism)</term><term>Binding Sites</term><term>Brain (drug effects)</term><term>Brain (metabolism)</term><term>Brain (pathology)</term><term>Corpus Striatum (drug effects)</term><term>Dopamine Agonists (pharmacology)</term><term>Drug Administration Schedule</term><term>Dyskinesia, Drug-Induced (metabolism)</term><term>Ergolines (pharmacology)</term><term>Female</term><term>GABA</term><term>GABA Antagonists (metabolism)</term><term>GABA-B Receptor Antagonists</term><term>Injections, Subcutaneous</term><term>Iodine Radioisotopes</term><term>Macaca fascicularis</term><term>Organophosphorus Compounds (metabolism)</term><term>Parkinson</term><term>Parkinson Disease, Secondary (chemically induced)</term><term>Parkinson Disease, Secondary (drug therapy)</term><term>Parkinson Disease, Secondary (metabolism)</term><term>Receptors, GABA-B (metabolism)</term><term>Substantia Nigra (drug effects)</term><term>Substantia Nigra (pathology)</term><term>Thalamus (drug effects)</term><term>Thalamus (metabolism)</term><term>Thalamus (pathology)</term><term>autoradiography</term><term>basal ganglia</term><term>dopamine agonist</term><term>dyskinesia</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Benzoates</term><term>GABA Antagonists</term><term>Organophosphorus Compounds</term><term>Receptors, GABA-B</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiparkinson Agents</term><term>Benzazepines</term><term>Dopamine Agonists</term><term>Ergolines</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>GABA-B Receptor Antagonists</term><term>Iodine Radioisotopes</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Basal Ganglia</term><term>Brain</term><term>Corpus Striatum</term><term>Substantia Nigra</term><term>Thalamus</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Basal Ganglia</term><term>Brain</term><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease, Secondary</term><term>Thalamus</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Basal Ganglia</term><term>Brain</term><term>Substantia Nigra</term><term>Thalamus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Autoradiography</term><term>Binding Sites</term><term>Drug Administration Schedule</term><term>Female</term><term>Injections, Subcutaneous</term><term>Macaca fascicularis</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Much evidence indicates that abnormal GABA neurotransmission may be implicated in the pathophysiology of Parkinson's disease (PD) and dopaminomimetic-induced dyskinesias (DID). In this study, autoradiography using 125I-CGP 64213 was performed to investigate GABAB receptor density in the brain of control monkeys as well as monkeys with MPTP-induced nigrostriatal depletion. Three MPTP monkeys received pulsatile administrations of the D1 dopamine (DA) receptor agonist (SKF 82958) whereas a long-acting D2 DA receptor agonist (cabergoline) was given to another three animals. SKF 82958 treatment relieved parkinsonian symptoms but two of three animals developed DID. Cabergoline induced a comparable motor benefit effect without persistent DID. 125I-CGP 64213 binding to GABAB receptors was heterogeneous throughout the brain with the highest levels in the medial habenula of the thalamus. MPTP induced a decrease (−40%) of 125I-CGP 64213 binding to GABAB receptors in the substantia nigra pars compacta (SNpc) and an increase (+29%) in the internal segment of the globus pallidus (GPi). This increase in the GPi was not affected by SKF 82958 but partly reversed by cabergoline. No change was seen in the striatum, the thalamus, the external segment of the globus pallidus, and the substantia nigra pars reticulata following MPTP and dopaminomimetic treatments. The changes of GABAB receptors observed in the SNpc and in the GPi suggest that alteration of GABAB receptors may play a role in the pathophysiology of PD and DID.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bédard">Paul J. Bédard</name><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><name sortKey="Goulet, Martin" sort="Goulet, Martin" uniqKey="Goulet M" first="Martin" last="Goulet">Martin Goulet</name><name sortKey="Grondin, Richard" sort="Grondin, Richard" uniqKey="Grondin R" first="Richard" last="Grondin">Richard Grondin</name><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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