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

Abstract Morphine 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 mor...

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Autores principales:	Alejandra Valderrama-Carvajal, Haritz Irizar, Belén Gago, Haritz Jiménez-Urbieta, Kjell Fuxe, María C. Rodríguez-Oroz, David Otaegui, Alicia Rivera
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bc34cc152564482a90c65b2b3ba4e09a
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spelling	oai:doaj.org-article:bc34cc152564482a90c65b2b3ba4e09a2021-12-02T16:07:51ZTranscriptomic integration of D4R and MOR signaling in the rat caudate putamen10.1038/s41598-018-25604-42045-2322https://doaj.org/article/bc34cc152564482a90c65b2b3ba4e09a2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25604-4https://doaj.org/toc/2045-2322Abstract Morphine 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.Alejandra Valderrama-CarvajalHaritz IrizarBelén GagoHaritz Jiménez-UrbietaKjell FuxeMaría C. Rodríguez-OrozDavid OtaeguiAlicia RiveraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alejandra Valderrama-Carvajal Haritz Irizar Belén Gago Haritz Jiménez-Urbieta Kjell Fuxe María C. Rodríguez-Oroz David Otaegui Alicia Rivera Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen
description	Abstract Morphine 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.
format	article
author	Alejandra Valderrama-Carvajal Haritz Irizar Belén Gago Haritz Jiménez-Urbieta Kjell Fuxe María C. Rodríguez-Oroz David Otaegui Alicia Rivera
author_facet	Alejandra Valderrama-Carvajal Haritz Irizar Belén Gago Haritz Jiménez-Urbieta Kjell Fuxe María C. Rodríguez-Oroz David Otaegui Alicia Rivera
author_sort	Alejandra Valderrama-Carvajal
title	Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen
title_short	Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen
title_full	Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen
title_fullStr	Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen
title_full_unstemmed	Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen
title_sort	transcriptomic integration of d4r and mor signaling in the rat caudate putamen
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/bc34cc152564482a90c65b2b3ba4e09a
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Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen

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