To access the full text documents, please follow this link: 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, Mireia; Mallol Montero, Josefa; Cortés Tejedor, Antonio; Casadó, Vicent; Lluís i Biset, Carme; Ferré, Sergi; Ortiz, Jordi; Canela Campos, Enric I.; McCormick, Peter J. |
| Other authors: | Universitat de Barcelona |
| 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. |
| Subject(s): | -Cocaïna -Receptors cel·lulars -Dopamina -Cocaine -Cell receptors -Dopamine |
| Rights: | cc-by-nc-sa (c) Moreno Guillén, Estefanía et al., 2014
http://creativecommons.org/licenses/by-nc-sa/3.0/es |
| Document type: | Article Article - Published version |
| Published by: | The Society for Neuroscience |
| Share: |
|
Related documents
Other documents of the same author
Moreno Guillén, Estefanía; Moreno-Delgado, David; Navarro Brugal, Gemma; Hoffmann, Hanne; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol Montero, Josefa; Cortés Tejedor, Antonio; Casadó, Vicent; Lluís i Biset, Carme; Ferré, Sergi; Ortiz, Jordi; Canela Campos, Enric I.; McCormick, Peter J.
Moreno Guillén, Estefanía; Hoffmann, Hanne; Gonzalez-Sepulveda, Marta; Navarro Brugal, Gemma; Casadó, Vicent; Cortés Tejedor, Antonio; Mallol Montero, Josefa; Vignes, Michel; McCormick, Peter J.; Canela Campos, Enric I.; Lluís i Biset, Carme; Moratalla, Rosario; Ferré, Sergi; Ortiz, Jordi; Franco Fernández, Rafael
Moreno Guillén, Estefanía; Hoffmann, Hanne; Gonzalez-Sepulveda, Marta; Navarro Brugal, Gemma; Casadó, Vicent; Cortés Tejedor, Antonio; Mallol Montero, Josefa; Vignes, Michel; McCormick, Peter J.; Canela Campos, Enric I.; Lluís i Biset, Carme; Moratalla, Rosario; Ferré, Sergi; Ortiz, Jordi; Franco Fernández, Rafael
Navarro Brugal, Gemma; Ferré, Sergi; Cordomí, Arnau; Moreno Guillén, Estefanía; Mallol Montero, Josefa; Casadó, Vicent; Cortés Tejedor, Antonio; Hoffmann, Hanne; Ortiz, Jordi; Canela Campos, Enric I.; Lluís i Biset, Carme; Pardo, Leonardo; Franco Fernández, Rafael; Woods, Amina S.
Navarro Brugal, Gemma; Ferré, Sergi; Cordomí, Arnau; Moreno Guillén, Estefanía; Mallol Montero, Josefa; Casadó, Vicent; Cortés Tejedor, Antonio; Hoffmann, Hanne; Ortiz, Jordi; Canela Campos, Enric I.; Lluís i Biset, Carme; Pardo, Leonardo; Franco Fernández, Rafael; Woods, Amina S.