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Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen.

dc.contributor.authorValderrama-Carvajal, Alejandra
dc.contributor.authorIrizar, Haritz
dc.contributor.authorGago, Belen
dc.contributor.authorJimenez-Urbieta, Haritz
dc.contributor.authorFuxe, Kjell
dc.contributor.authorRodriguez-Oroz, Maria C
dc.contributor.authorOtaegui, David
dc.contributor.authorRivera, Alicia
dc.contributor.funderJunta de Andalucía
dc.contributor.funderGobierno Vasco
dc.date.accessioned2023-01-25T10:08:22Z
dc.date.available2023-01-25T10:08:22Z
dc.date.issued2018-04-20
dc.description.abstractMorphine binding to opioid receptors, mainly to μ opioid receptor (MOR), induces alterations in intracellular pathways essential to the initial development of addiction. The activation of the dopamine D4 receptor (D4R), which is expressed in the caudate putamen (CPu), mainly counteracts morphine-induced alterations in several molecular networks. These involve transcription factors, adaptive changes of MOR signaling, activation of the nigrostriatal dopamine pathway and behavioural effects, underlining functional D4R/MOR interactions. To shed light on the molecular mechanisms implicated, we evaluated the transcriptome alterations following acute administration of morphine and/or PD168,077 (D4R agonist) using whole-genome microarrays and a linear regression-based differential expression analysis. The results highlight the development of a unique transcriptional signature following the co-administration of both drugs that reflects a countereffect of PD168,077 on morphine effects. A KEGG pathway enrichment analysis using GSEA identified 3 pathways enriched positively in morphine vs control and negatively in morphine + PD168,077 vs morphine (Ribosome, Complement and Coagulation Cascades, Systemic Lupus Erythematosus) and 3 pathways with the opposite enrichment pattern (Alzheimer's Disease, Neuroactive Ligand Receptor Interaction, Oxidative Phosphorilation). This work supports the massive D4R/MOR functional integration at the CPu and provides a gateway to further studies on the use of D4R drugs to modulate morphine-induced effects.
dc.description.sponsorshipThis work was supported by the Junta de Andalucía grant (CTS-0161) and Universidad de Málaga. Dr. Valderrama-Carvajal’s work has been funded by a Junta de Andalucía Ph.D. Studentship Grant. Dr Irizar and Haritz Jiménez-Urbieta were supported by a Gobierno Vasco Ph.D. Studentship Grant.
dc.description.versionSi
dc.identifier.citationValderrama-Carvajal A, Irizar H, Gago B, Jiménez-Urbieta H, Fuxe K, Rodríguez-Oroz MC, et al. Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen. Sci Rep. 2018 May 9;8(1):7337
dc.identifier.doi10.1038/s41598-018-25604-4
dc.identifier.essn2045-2322
dc.identifier.pmcPMC5943359
dc.identifier.pmid29743514
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943359/pdf
dc.identifier.unpaywallURLhttps://www.nature.com/articles/s41598-018-25604-4.pdf
dc.identifier.urihttp://hdl.handle.net/10668/12440
dc.issue.number1
dc.journal.titleScientific reports
dc.journal.titleabbreviationSci Rep
dc.language.isoen
dc.organizationIBIMA
dc.page.number9
dc.provenanceRealizada la curación de contenido 09/08/2024
dc.publisherSpringer Nature
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDCTS-0161
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-018-25604-4
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAnalgesics
dc.subjectBenzamides
dc.subjectDopamine agonists
dc.subjectRats
dc.subjectReceptors
dc.subject.decsAgonistas de dopamina
dc.subject.decsAnalgésicos opioides
dc.subject.decsAnimales
dc.subject.decsBenzamidas
dc.subject.decsExpresión génica
dc.subject.decsMasculino
dc.subject.decsMorfina
dc.subject.decsNúcleo caudado
dc.subject.decsPiperazinas
dc.subject.decsReceptores de dopamina D4
dc.subject.decsTranscriptoma
dc.subject.decsTransducción de señal
dc.subject.meshAnalgesics, opioid
dc.subject.meshAnimals
dc.subject.meshBenzamides
dc.subject.meshCaudate nucleus
dc.subject.meshDopamine agonists
dc.subject.meshGene expression
dc.subject.meshMale
dc.subject.meshMorphine
dc.subject.meshPiperazines
dc.subject.meshPutamen
dc.subject.meshRats
dc.subject.meshRats, sprague-dawley
dc.subject.meshReceptors, dopamine D4
dc.subject.meshReceptors, opioid
dc.subject.meshSignal transduction
dc.subject.meshTranscriptome
dc.titleTranscriptomic integration of D4R and MOR signaling in the rat caudate putamen.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number8
dspace.entity.typePublication

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