Nociceptin/orphanin FQ receptor agonists attenuate L-DOPA-induced dyskinesias
Identifieur interne : 000804 ( Hal/Corpus ); précédent : 000803; suivant : 000805Nociceptin/orphanin FQ receptor agonists attenuate L-DOPA-induced dyskinesias
Auteurs : Matteo Marti ; Donata Rodi ; Q. Li ; Remo Guerrini ; Stefania Fasano ; Ilaria Morella ; Alessandro Tozzi ; Riccardo Brambilla ; Paolo Calabresi ; Michele Simonato ; Erwan Bezard ; Michele MorariSource :
- Journal of Neuroscience [ 0270-6474 ] ; 2012-11-14.
Abstract
In the present study we investigated whether the neuropeptide nociceptin/orphanin FQ (N/OFQ), previously implicated in the pathogenesis of Parkinson's disease, also affects L-DOPA-induced dyskinesia. In striatal slices of naive rodents, N/OFQ (0.1-1 μm) prevented the increase of ERK phosphorylation and the loss of depotentiation of synaptic plasticity induced by the D1 receptor agonist SKF38393 in spiny neurons. In vivo, exogenous N/OFQ (0.03-1 nmol, i.c.v.) or a synthetic N/OFQ receptor agonist given systemically (0.01-1 mg/Kg) attenuated dyskinesias expression in 6-hydroxydopamine hemilesioned rats primed with L-DOPA, without causing primary hypolocomotive effects. Conversely, N/OFQ receptor antagonists worsened dyskinesia expression. In vivo microdialysis revealed that N/OFQ prevented dyskinesias simultaneously with its neurochemical correlates such as the surge of nigral GABA and glutamate, and the reduction of thalamic GABA. Regional microinjections revealed that N/OFQ attenuated dyskinesias more potently and effectively when microinjected in striatum than substantia nigra (SN) reticulata, whereas N/OFQ receptor antagonists were ineffective in striatum but worsened dyskinesias when given in SN. Quantitative autoradiography showed an increase in N/OFQ receptor binding in striatum and a reduction in SN of both unprimed and dyskinetic 6-hydroxydopamine rats, consistent with opposite adaptive changes of N/OFQ transmission. Finally, the N/OFQ receptor synthetic agonist also reduced dyskinesia expression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated dyskinetic macaques without affecting the global parkinsonian score. We conclude that N/OFQ receptor agonists may represent a novel strategy to counteract L-DOPA-induced dyskinesias. Their action is possibly mediated by upregulated striatal N/OFQ receptors opposing the D1 receptor-mediated overactivation of the striatonigral direct pathway.
Url:
DOI: 10.1523/JNEUROSCI.6408-11.2012
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Li</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-253183" status="INCOMING"><orgName>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China</orgName><desc><address><country key="CN"></country></address></desc><listRelation><relation active="#struct-360502" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-360502" type="direct"><org type="institution" xml:id="struct-360502" status="INCOMING"><orgName>China Academy of Medical Sciences, Beijing, China</orgName><desc><address><country key="FR"></country></address></desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Guerrini, Remo" sort="Guerrini, Remo" uniqKey="Guerrini R" first="Remo" last="Guerrini">Remo Guerrini</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-262640" status="INCOMING"><orgName>Department of Pharmaceutical Sciences</orgName><desc><address><addrLine>Ferrara</addrLine><country key="IT"></country></address></desc><listRelation><relation active="#struct-54905" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-54905" type="direct"><org type="institution" xml:id="struct-54905" status="VALID"><orgName>University of Ferrara [Ferrara]</orgName><desc><address><addrLine>Via Savonarola, 9, 44121 Ferrara FE</addrLine><country key="IT"></country></address><ref type="url">http://unife.it/</ref></desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Fasano, Stefania" sort="Fasano, Stefania" uniqKey="Fasano S" first="Stefania" last="Fasano">Stefania Fasano</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-262421" status="INCOMING"><orgName>Institute of Experimental Neurology</orgName><desc><address><addrLine>Division of Neuroscience, San Raffaele Research Institute, Milan</addrLine><country key="IT"></country></address></desc><listRelation><relation active="#struct-362278" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-362278" type="direct"><org type="institution" xml:id="struct-362278" status="INCOMING"><orgName>San Raffaele Research Institute, Milan</orgName><desc><address><country key="FR"></country></address></desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Morella, Ilaria" sort="Morella, Ilaria" uniqKey="Morella I" first="Ilaria" last="Morella">Ilaria Morella</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-262421" status="INCOMING"><orgName>Institute of Experimental Neurology</orgName><desc><address><addrLine>Division of Neuroscience, San Raffaele Research Institute, Milan</addrLine><country key="IT"></country></address></desc><listRelation><relation active="#struct-362278" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-362278" type="direct"><org type="institution" xml:id="struct-362278" status="INCOMING"><orgName>San Raffaele Research Institute, Milan</orgName><desc><address><country key="FR"></country></address></desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Tozzi, Alessandro" sort="Tozzi, Alessandro" uniqKey="Tozzi A" first="Alessandro" last="Tozzi">Alessandro Tozzi</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-262641" status="INCOMING"><orgName>Clinica Neurologica</orgName><desc><address><addrLine>Dip. Specialità Medico-Chirurgiche e Sanità Pubblica, Università di Perugia, Ospedale Santa Maria della Misericordia, 06123 Perugia</addrLine><country key="IT"></country></address></desc><listRelation><relation active="#struct-318622" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-318622" type="direct"><org type="institution" xml:id="struct-318622" status="INCOMING"><orgName>Università di Perugia</orgName><desc><address><country key="FR"></country></address></desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Brambilla, Riccardo" sort="Brambilla, Riccardo" uniqKey="Brambilla R" first="Riccardo" last="Brambilla">Riccardo Brambilla</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-262421" status="INCOMING"><orgName>Institute of Experimental Neurology</orgName><desc><address><addrLine>Division of Neuroscience, San Raffaele Research Institute, Milan</addrLine><country key="IT"></country></address></desc><listRelation><relation active="#struct-362278" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-362278" type="direct"><org type="institution" xml:id="struct-362278" status="INCOMING"><orgName>San Raffaele Research Institute, Milan</orgName><desc><address><country key="FR"></country></address></desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Calabresi, Paolo" sort="Calabresi, Paolo" uniqKey="Calabresi P" first="Paolo" last="Calabresi">Paolo Calabresi</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-262641" status="INCOMING"><orgName>Clinica Neurologica</orgName><desc><address><addrLine>Dip. Specialità Medico-Chirurgiche e Sanità Pubblica, Università di Perugia, Ospedale Santa Maria della Misericordia, 06123 Perugia</addrLine><country key="IT"></country></address></desc><listRelation><relation active="#struct-318622" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-318622" type="direct"><org type="institution" xml:id="struct-318622" status="INCOMING"><orgName>Università di Perugia</orgName><desc><address><country key="FR"></country></address></desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Simonato, Michele" sort="Simonato, Michele" uniqKey="Simonato M" first="Michele" last="Simonato">Michele Simonato</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-225601" status="INCOMING"><orgName>Department of Clinical and Experimental Medicine (Section of Pharmacology) and Neuroscience Center</orgName><desc><address><addrLine>44100 Ferrara</addrLine><country key="IT"></country></address></desc><listRelation><relation active="#struct-54905" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-54905" type="direct"><org type="institution" xml:id="struct-54905" status="VALID"><orgName>University of Ferrara [Ferrara]</orgName><desc><address><addrLine>Via Savonarola, 9, 44121 Ferrara FE</addrLine><country key="IT"></country></address><ref type="url">http://unife.it/</ref></desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-244085" status="VALID"> <orgName>Institut des Maladies Neurodégénératives [Bordeaux]</orgName> <orgName type="acronym">IMN</orgName> <desc> <address> <addrLine>Bât. 3b 1er étage 146 Rue Léo Saignat 33076 Bordeaux </addrLine> <country key="FR"></country> </address> <ref type="url">http://imn-bordeaux.org/</ref> </desc> <listRelation> <relation active="#struct-259761" type="direct"></relation> <relation name="UMR5293" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-259761" type="direct"><org type="institution" xml:id="struct-259761" status="VALID"> <orgName>Université de Bordeaux</orgName> <orgName type="acronym">UB</orgName> <desc> <address> <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.u-bordeaux.fr/</ref> </desc></org></tutelle><tutelle name="UMR5293" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Morari, Michele" sort="Morari, Michele" uniqKey="Morari M" first="Michele" last="Morari">Michele Morari</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-262263" status="INCOMING"><orgName>Department of Medical Sciences</orgName><desc><address><addrLine>Section of Pharmacology University of Ferrara Ferrara</addrLine><country key="IT"></country></address></desc><listRelation><relation active="#struct-54905" type="direct"></relation></listRelation><tutelles><tutelle active="#struct-54905" type="direct"><org type="institution" xml:id="struct-54905" status="VALID"><orgName>University of Ferrara [Ferrara]</orgName><desc><address><addrLine>Via Savonarola, 9, 44121 Ferrara FE</addrLine><country key="IT"></country></address><ref type="url">http://unife.it/</ref></desc></org></tutelle></tutelles></hal:affiliation></affiliation></author></analytic><idno type="DOI">10.1523/JNEUROSCI.6408-11.2012</idno><series><title level="j">Journal of Neuroscience</title><idno type="ISSN">0270-6474</idno><imprint><date type="datePub">2012-11-14</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In the present study we investigated whether the neuropeptide nociceptin/orphanin FQ (N/OFQ), previously implicated in the pathogenesis of Parkinson's disease, also affects L-DOPA-induced dyskinesia. In striatal slices of naive rodents, N/OFQ (0.1-1 μm) prevented the increase of ERK phosphorylation and the loss of depotentiation of synaptic plasticity induced by the D1 receptor agonist SKF38393 in spiny neurons. In vivo, exogenous N/OFQ (0.03-1 nmol, i.c.v.) or a synthetic N/OFQ receptor agonist given systemically (0.01-1 mg/Kg) attenuated dyskinesias expression in 6-hydroxydopamine hemilesioned rats primed with L-DOPA, without causing primary hypolocomotive effects. Conversely, N/OFQ receptor antagonists worsened dyskinesia expression. In vivo microdialysis revealed that N/OFQ prevented dyskinesias simultaneously with its neurochemical correlates such as the surge of nigral GABA and glutamate, and the reduction of thalamic GABA. Regional microinjections revealed that N/OFQ attenuated dyskinesias more potently and effectively when microinjected in striatum than substantia nigra (SN) reticulata, whereas N/OFQ receptor antagonists were ineffective in striatum but worsened dyskinesias when given in SN. Quantitative autoradiography showed an increase in N/OFQ receptor binding in striatum and a reduction in SN of both unprimed and dyskinetic 6-hydroxydopamine rats, consistent with opposite adaptive changes of N/OFQ transmission. Finally, the N/OFQ receptor synthetic agonist also reduced dyskinesia expression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated dyskinetic macaques without affecting the global parkinsonian score. We conclude that N/OFQ receptor agonists may represent a novel strategy to counteract L-DOPA-induced dyskinesias. Their action is possibly mediated by upregulated striatal N/OFQ receptors opposing the D1 receptor-mediated overactivation of the striatonigral direct pathway.</div></front></TEI><hal api="V3"><titleStmt><title xml:lang="en">Nociceptin/orphanin FQ receptor agonists attenuate L-DOPA-induced dyskinesias</title><author role="aut"><persName><forename type="first">Matteo</forename><surname>Marti</surname></persName><idno type="halauthorid">1059377</idno><affiliation ref="#struct-262260"></affiliation></author><author role="aut"><persName><forename type="first">Donata</forename><surname>Rodi</surname></persName><idno type="halauthorid">1061158</idno><affiliation ref="#struct-262260"></affiliation></author><author role="aut"><persName><forename type="first">Q.</forename><surname>Li</surname></persName><idno type="halauthorid">11257</idno><affiliation ref="#struct-253183"></affiliation></author><author role="aut"><persName><forename type="first">Remo</forename><surname>Guerrini</surname></persName><idno type="halauthorid">1061159</idno><affiliation ref="#struct-262640"></affiliation></author><author role="aut"><persName><forename type="first">Stefania</forename><surname>Fasano</surname></persName><idno type="halauthorid">1060301</idno><affiliation ref="#struct-262421"></affiliation></author><author role="aut"><persName><forename type="first">Ilaria</forename><surname>Morella</surname></persName><idno type="halauthorid">1061160</idno><affiliation ref="#struct-262421"></affiliation></author><author role="aut"><persName><forename type="first">Alessandro</forename><surname>Tozzi</surname></persName><idno type="halauthorid">1061161</idno><affiliation ref="#struct-262641"></affiliation></author><author role="aut"><persName><forename type="first">Riccardo</forename><surname>Brambilla</surname></persName><idno type="halauthorid">1061176</idno><affiliation ref="#struct-262421"></affiliation></author><author role="aut"><persName><forename type="first">Paolo</forename><surname>Calabresi</surname></persName><idno type="halauthorid">523226</idno><affiliation ref="#struct-262641"></affiliation></author><author role="aut"><persName><forename type="first">Michele</forename><surname>Simonato</surname></persName><idno type="halauthorid">863803</idno><affiliation ref="#struct-225601"></affiliation></author><author role="aut"><persName><forename type="first">Erwan</forename><surname>Bezard</surname></persName><email type="md5">b0deb6c343e8d1ae022cfd4a58cecc43</email><email type="domain">u-bordeaux2.fr</email><idno type="halauthorid">506531</idno><affiliation ref="#struct-244085"></affiliation></author><author role="crp"><persName><forename type="first">Michele</forename><surname>Morari</surname></persName><email type="md5">3ee31fcfa8027909d4ec586e6a4eb7cc</email><email type="domain">unife.it</email><idno type="halauthorid">1061163</idno><affiliation ref="#struct-262263"></affiliation></author><editor role="depositor"><persName><forename>Catherine</forename><surname>Griveau</surname></persName><email type="md5">2721a25e4c55ec4e1a64e00a1898f5bc</email><email type="domain">u-bordeaux.fr</email></editor></titleStmt><editionStmt><edition n="v1" type="current"><date type="whenSubmitted">2014-07-30 11:20:58</date><date type="whenModified">2014-07-30 11:39:23</date><date type="whenReleased">2014-07-30 11:39:23</date><date type="whenProduced">2012-11-14</date><date type="whenEndEmbargoed">2014-07-30</date><ref type="file" target="https://hal.archives-ouvertes.fr/hal-01053293/document"><date notBefore="2014-07-30"></date></ref><ref type="file" subtype="greenPublisher" n="1" target="https://hal.archives-ouvertes.fr/hal-01053293/file/Nociceptin-orphanin_FQ_receptor_agonists_attenuate_L-DOPA-induced_dyskinesias.pdf"><date notBefore="2014-07-30"></date></ref></edition><respStmt><resp>contributor</resp><name key="194354"><persName><forename>Catherine</forename><surname>Griveau</surname></persName><email type="md5">2721a25e4c55ec4e1a64e00a1898f5bc</email><email type="domain">u-bordeaux.fr</email></name></respStmt></editionStmt><publicationStmt><distributor>CCSD</distributor><idno type="halId">hal-01053293</idno><idno type="halUri">https://hal.archives-ouvertes.fr/hal-01053293</idno><idno type="halBibtex">marti:hal-01053293</idno><idno type="halRefHtml">Journal of Neuroscience, Society for Neuroscience, 2012, 32 (46), pp.16106-16119. <10.1523/JNEUROSCI.6408-11.2012></idno><idno type="halRef">Journal of Neuroscience, Society for Neuroscience, 2012, 32 (46), pp.16106-16119. <10.1523/JNEUROSCI.6408-11.2012></idno></publicationStmt><seriesStmt><idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno></seriesStmt><notesStmt><note type="audience" n="2">International</note><note type="popular" n="0">No</note><note type="peer" n="1">Yes</note></notesStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Nociceptin/orphanin FQ receptor agonists attenuate L-DOPA-induced dyskinesias</title><author role="aut"><persName><forename type="first">Matteo</forename><surname>Marti</surname></persName><idno type="halauthorid">1059377</idno><affiliation ref="#struct-262260"></affiliation></author><author role="aut"><persName><forename type="first">Donata</forename><surname>Rodi</surname></persName><idno type="halauthorid">1061158</idno><affiliation ref="#struct-262260"></affiliation></author><author role="aut"><persName><forename type="first">Q.</forename><surname>Li</surname></persName><idno type="halauthorid">11257</idno><affiliation ref="#struct-253183"></affiliation></author><author role="aut"><persName><forename type="first">Remo</forename><surname>Guerrini</surname></persName><idno type="halauthorid">1061159</idno><affiliation ref="#struct-262640"></affiliation></author><author role="aut"><persName><forename type="first">Stefania</forename><surname>Fasano</surname></persName><idno type="halauthorid">1060301</idno><affiliation ref="#struct-262421"></affiliation></author><author role="aut"><persName><forename type="first">Ilaria</forename><surname>Morella</surname></persName><idno type="halauthorid">1061160</idno><affiliation ref="#struct-262421"></affiliation></author><author role="aut"><persName><forename type="first">Alessandro</forename><surname>Tozzi</surname></persName><idno type="halauthorid">1061161</idno><affiliation ref="#struct-262641"></affiliation></author><author role="aut"><persName><forename type="first">Riccardo</forename><surname>Brambilla</surname></persName><idno type="halauthorid">1061176</idno><affiliation ref="#struct-262421"></affiliation></author><author role="aut"><persName><forename type="first">Paolo</forename><surname>Calabresi</surname></persName><idno type="halauthorid">523226</idno><affiliation ref="#struct-262641"></affiliation></author><author role="aut"><persName><forename type="first">Michele</forename><surname>Simonato</surname></persName><idno type="halauthorid">863803</idno><affiliation ref="#struct-225601"></affiliation></author><author role="aut"><persName><forename type="first">Erwan</forename><surname>Bezard</surname></persName><email type="md5">b0deb6c343e8d1ae022cfd4a58cecc43</email><email type="domain">u-bordeaux2.fr</email><idno type="halauthorid">506531</idno><affiliation ref="#struct-244085"></affiliation></author><author role="crp"><persName><forename type="first">Michele</forename><surname>Morari</surname></persName><email type="md5">3ee31fcfa8027909d4ec586e6a4eb7cc</email><email type="domain">unife.it</email><idno type="halauthorid">1061163</idno><affiliation ref="#struct-262263"></affiliation></author></analytic><monogr><idno type="halJournalId" status="VALID">6330</idno><idno type="issn">0270-6474</idno><idno type="eissn">1529-2401</idno><title level="j">Journal of Neuroscience</title><imprint><publisher>Society for Neuroscience</publisher><biblScope unit="volume">32</biblScope><biblScope unit="issue">46</biblScope><biblScope unit="pp">16106-16119</biblScope><date type="datePub">2012-11-14</date></imprint></monogr><idno type="doi">10.1523/JNEUROSCI.6408-11.2012</idno><idno type="pubmed">23152595</idno></biblStruct></sourceDesc><profileDesc><langUsage><language ident="en">English</language></langUsage><textClass><classCode scheme="halDomain" n="scco.neur">Cognitive science/Neuroscience</classCode><classCode scheme="halTypology" n="ART">Journal articles</classCode></textClass><abstract xml:lang="en">In the present study we investigated whether the neuropeptide nociceptin/orphanin FQ (N/OFQ), previously implicated in the pathogenesis of Parkinson's disease, also affects L-DOPA-induced dyskinesia. In striatal slices of naive rodents, N/OFQ (0.1-1 μm) prevented the increase of ERK phosphorylation and the loss of depotentiation of synaptic plasticity induced by the D1 receptor agonist SKF38393 in spiny neurons. In vivo, exogenous N/OFQ (0.03-1 nmol, i.c.v.) or a synthetic N/OFQ receptor agonist given systemically (0.01-1 mg/Kg) attenuated dyskinesias expression in 6-hydroxydopamine hemilesioned rats primed with L-DOPA, without causing primary hypolocomotive effects. Conversely, N/OFQ receptor antagonists worsened dyskinesia expression. In vivo microdialysis revealed that N/OFQ prevented dyskinesias simultaneously with its neurochemical correlates such as the surge of nigral GABA and glutamate, and the reduction of thalamic GABA. Regional microinjections revealed that N/OFQ attenuated dyskinesias more potently and effectively when microinjected in striatum than substantia nigra (SN) reticulata, whereas N/OFQ receptor antagonists were ineffective in striatum but worsened dyskinesias when given in SN. Quantitative autoradiography showed an increase in N/OFQ receptor binding in striatum and a reduction in SN of both unprimed and dyskinetic 6-hydroxydopamine rats, consistent with opposite adaptive changes of N/OFQ transmission. Finally, the N/OFQ receptor synthetic agonist also reduced dyskinesia expression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated dyskinetic macaques without affecting the global parkinsonian score. We conclude that N/OFQ receptor agonists may represent a novel strategy to counteract L-DOPA-induced dyskinesias. Their action is possibly mediated by upregulated striatal N/OFQ receptors opposing the D1 receptor-mediated overactivation of the striatonigral direct pathway.</abstract></profileDesc></hal></record>Pour manipuler ce document sous Unix (Dilib)
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