RT Journal Article
T1 Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen.
A1 Valderrama-Carvajal, Alejandra
A1 Irizar, Haritz
A1 Gago, Belen
A1 Jimenez-Urbieta, Haritz
A1 Fuxe, Kjell
A1 Rodriguez-Oroz, Maria C
A1 Otaegui, David
A1 Rivera, Alicia
K1 Analgesics
K1 Benzamides
K1 Dopamine agonists
K1 Rats
K1 Receptors
AB 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.
PB Springer Nature
YR 2018
FD 2018-04-20
LK http://hdl.handle.net/10668/12440
UL http://hdl.handle.net/10668/12440
LA en
NO Valderrama-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
NO This 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.
DS RISalud
RD Apr 10, 2025