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http://hdl.handle.net/2445/122586
Title: | Cocaine disrupts histamine H3 receptor modulation of dopamine D1 receptor signaling: σ1-D1-H3 receptor complexes as key targets for reducing cocaine's effects |
Author: | Moreno Guillén, Estefanía Moreno-Delgado, David Navarro Brugal, Gemma Hoffmann, Hanne Fuentes, Silvia Rosell-Vilar, Santi Gasperini, Paola Rodríguez Ruiz, Mar Medrano Moya, Mireia Mallol Montero, Josefa Cortés Tejedor, Antonio Casadó, Vicent Lluís i Biset, Carme Ferré, Sergi Ortiz, Jordi Canela Campos, Enric I. McCormick, Peter J. |
Keywords: | Cocaïna Receptors cel·lulars Dopamina Cocaine Cell receptors Dopamine |
Issue Date: | 5-Mar-2014 |
Publisher: | The Society for Neuroscience |
Abstract: | The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. |
Note: | Reproducció del document publicat a: https://doi.org/10.1523/JNEUROSCI.4147-13.2014 |
It is part of: | Journal of Neuroscience, 2014, vol. 34, num. 10, p. 3545-3558 |
URI: | http://hdl.handle.net/2445/122586 |
Related resource: | https://doi.org/10.1523/JNEUROSCI.4147-13.2014 |
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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