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Title: Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine
Author: 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.
Ferré, Sergi
McCormick, Peter J.
Keywords: Receptors cel·lulars
Cell receptors
Issue Date: 29-Apr-2015
Publisher: The Society for Neuroscience
Abstract: 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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It is part of: Journal of Neuroscience, 2015, vol. 35, num. 17, p. 6639-6653
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ISSN: 0270-6474
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Bioquímica i Fisiologia)

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