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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/122634
Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine
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Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target sigma1 receptor (sigma1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the sigma1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking.
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NAVARRO BRUGAL, Gemma, QUIROZ, César, MORENO-DELGADO, David, SIERAKOWIAK, Adam, MCDOWELL, Kimberly, MORENO GUILLÉN, Estefanía, REA, William, CAI, Ning-sheng, AGUINAGA ANDRÉS, David, HOWELL, Lesley a., HAUSCH, Felix, CORTÉS TEJEDOR, Antonio, MALLOL MONTERO, Josefa, CASADÓ, Vicent, LLUÍS I BISET, Carme, CANELA CAMPOS, Enric i. (enric isidre), FERRÉ, Sergi, MCCORMICK, Peter j.. Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine. _Journal of Neuroscience_. 2015. Vol. 35, núm. 17, pàgs. 6639-6653. [consulta: 30 de gener de 2026]. ISSN: 0270-6474. [Disponible a: https://hdl.handle.net/2445/122634]