Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/122634
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 Cocaïna Cell receptors Cocaine |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1523/JNEUROSCI.4364-14.2015 |
It is part of: | Journal of Neuroscience, 2015, vol. 35, num. 17, p. 6639-6653 |
URI: | http://hdl.handle.net/2445/122634 |
Related resource: | https://doi.org/10.1523/JNEUROSCI.4364-14.2015 |
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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