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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, et al. Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine. Journal of Neuroscience. 2015. Vol. 35, num. 17, pags. 6639-6653. ISSN 0270-6474. [consulted: 9 of September of 2026]. Available at: https://hdl.handle.net/2445/122634