Please use this identifier to cite or link to this item:
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
Cell receptors
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:
It is part of: Journal of Neuroscience, 2014, vol. 34, num. 10, p. 3545-3558
Related resource:
ISSN: 0270-6474
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Bioquímica i Fisiologia)

Files in This Item:
File Description SizeFormat 
634916.pdf3.38 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons