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dc.contributor | Universitat de Barcelona |
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dc.contributor.author | Moreno Guillén, Estefanía |
dc.contributor.author | Moreno-Delgado, David |
dc.contributor.author | Navarro Brugal, Gemma |
dc.contributor.author | Hoffmann, Hanne |
dc.contributor.author | Fuentes, Silvia |
dc.contributor.author | Rosell-Vilar, Santi |
dc.contributor.author | Gasperini, Paola |
dc.contributor.author | Rodríguez-Ruiz, Mar |
dc.contributor.author | Medrano, Mireia |
dc.contributor.author | Mallol Montero, Josefa |
dc.contributor.author | Cortés Tejedor, Antonio |
dc.contributor.author | Casadó, Vicent |
dc.contributor.author | Lluís i Biset, Carme |
dc.contributor.author | Ferré, Sergi |
dc.contributor.author | Ortiz, Jordi |
dc.contributor.author | Canela Campos, Enric I. |
dc.contributor.author | McCormick, Peter J. |
dc.date | 2018-05-25T17:39:32Z |
dc.date | 2018-05-25T17:39:32Z |
dc.date | 2014-03-05 |
dc.date | 2018-05-25T17:39:33Z |
dc.identifier.citation | 0270-6474 |
dc.identifier.citation | 634916 |
dc.identifier.uri | http://hdl.handle.net/2445/122586 |
dc.description.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. |
dc.format | 14 p. |
dc.format | application/pdf |
dc.language.iso | eng |
dc.publisher | The Society for Neuroscience |
dc.relation | Reproducció del document publicat a: https://doi.org/10.1523/JNEUROSCI.4147-13.2014 |
dc.relation | Journal of Neuroscience, 2014, vol. 34, num. 10, p. 3545-3558 |
dc.relation | https://doi.org/10.1523/JNEUROSCI.4147-13.2014 |
dc.rights | cc-by-nc-sa (c) Moreno Guillén, Estefanía et al., 2014 |
dc.rights | info:eu-repo/semantics/openAccess |
dc.rights | http://creativecommons.org/licenses/by-nc-sa/3.0/es |
dc.subject | Cocaïna |
dc.subject | Receptors cel·lulars |
dc.subject | Dopamina |
dc.subject | Cocaine |
dc.subject | Cell receptors |
dc.subject | Dopamine |
dc.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 |
dc.type | info:eu-repo/semantics/article |
dc.type | info:eu-repo/semantics/publishedVersion |