A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior

Hypocretin/orexin signaling is critically involved in relapse to drug-seeking behaviors. In this study, we investigated the involvement of the hypocretin system in the reinstatement of nicotine-seeking behavior induced by nicotine-associated cues. Pretreatment with the hypocretin receptor-1 antagoni...

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Detalles Bibliográficos
Autores: Plaza-Zabala, Ainhoa, 1982-, Flores de los Heros, África, 1985-, Martín García, Elena, 1975-, Saravia Santos, Rocio, 1988-, Maldonado, Rafael, 1961-, Berrendero Díaz, Fernando, 1971-
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/23306
Acceso en línea:http://hdl.handle.net/10230/23306
http://dx.doi.org/10.1038/npp.2013.72
Access Level:acceso abierto
Palabra clave:Nicotina -- Addicció
Nicotina -- Farmacologia
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spelling A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behaviorPlaza-Zabala, Ainhoa, 1982-Flores de los Heros, África, 1985-Martín García, Elena, 1975-Saravia Santos, Rocio, 1988-Maldonado, Rafael, 1961-Berrendero Díaz, Fernando, 1971-Nicotina -- AddiccióNicotina -- FarmacologiaHypocretin/orexin signaling is critically involved in relapse to drug-seeking behaviors. In this study, we investigated the involvement of the hypocretin system in the reinstatement of nicotine-seeking behavior induced by nicotine-associated cues. Pretreatment with the hypocretin receptor-1 antagonist SB334867, but not with the hypocretin receptor-2 antagonist TCSOX229, attenuated cue-induced reinstatement of nicotine-seeking, which was associated with an activation of hypocretin neurons of the lateral and perifornical hypothalamic areas. In addition, relapse to nicotine-seeking increased the phosphorylation levels of GluR2-Ser880, NR1-Ser890, and p38 MAPK in the nucleus accumbens (NAc), but not in the prefrontal cortex. Notably, phosphorylation levels of NR1-Ser890 and p38 MAPK, but not GluR2-Ser880, were dependent on hypocretin receptor-1 activation. The intra-accumbens infusion of the protein kinase C (PKC) inhibitor NPC-15437 reduced nicotine-seeking behavior elicited by drug-paired cues consistent with the PKC-dependent phosphorylations of GluR2-Ser880 and NR1-Ser890. SB334867 failed to modify cue-induced reinstatement of food-seeking, which did not produce any biochemical changes in the NAc. These data identify hypocretin receptor-1 and PKC signaling as potential targets for the treatment of relapse to nicotine-seeking induced by nicotine-associated cues.This work was supported by the Instituto de Salud Carlos III grants, #PI07/0559, #PI10/00316 and #RD06/001/001 (RTA-RETICS), by the Spanish Ministry of Science and Technology, Consolider-C #SAF2007-64062 and #SAF2011-29864, the Catalan Government (SGR2009-00731), and by the Catalan Institution for Research and Advanced Studies (ICREA Academia program). Ainhoa Plaza-Zabala and África Flores are recipients of a predoctoral fellowship from the Spanish Ministry of EducationNature Publishing Group201520152013info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/23306http://dx.doi.org/10.1038/npp.2013.72reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNeuropsychopharmacology. 2013 Aug;38(9):1724-36info:eu-repo/grantAgreement/ES/3PN/SAF2011-29864info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062© Nature Publishing Group. http://dx.doi.org/10.1038/npp.2013.72info:eu-repo/semantics/openAccessoai:recercat.cat:10230/233062026-05-29T05:05:01Z
dc.title.none.fl_str_mv A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior
title A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior
spellingShingle A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior
Plaza-Zabala, Ainhoa, 1982-
Nicotina -- Addicció
Nicotina -- Farmacologia
title_short A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior
title_full A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior
title_fullStr A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior
title_full_unstemmed A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior
title_sort A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior
dc.creator.none.fl_str_mv Plaza-Zabala, Ainhoa, 1982-
Flores de los Heros, África, 1985-
Martín García, Elena, 1975-
Saravia Santos, Rocio, 1988-
Maldonado, Rafael, 1961-
Berrendero Díaz, Fernando, 1971-
author Plaza-Zabala, Ainhoa, 1982-
author_facet Plaza-Zabala, Ainhoa, 1982-
Flores de los Heros, África, 1985-
Martín García, Elena, 1975-
Saravia Santos, Rocio, 1988-
Maldonado, Rafael, 1961-
Berrendero Díaz, Fernando, 1971-
author_role author
author2 Flores de los Heros, África, 1985-
Martín García, Elena, 1975-
Saravia Santos, Rocio, 1988-
Maldonado, Rafael, 1961-
Berrendero Díaz, Fernando, 1971-
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Nicotina -- Addicció
Nicotina -- Farmacologia
topic Nicotina -- Addicció
Nicotina -- Farmacologia
description Hypocretin/orexin signaling is critically involved in relapse to drug-seeking behaviors. In this study, we investigated the involvement of the hypocretin system in the reinstatement of nicotine-seeking behavior induced by nicotine-associated cues. Pretreatment with the hypocretin receptor-1 antagonist SB334867, but not with the hypocretin receptor-2 antagonist TCSOX229, attenuated cue-induced reinstatement of nicotine-seeking, which was associated with an activation of hypocretin neurons of the lateral and perifornical hypothalamic areas. In addition, relapse to nicotine-seeking increased the phosphorylation levels of GluR2-Ser880, NR1-Ser890, and p38 MAPK in the nucleus accumbens (NAc), but not in the prefrontal cortex. Notably, phosphorylation levels of NR1-Ser890 and p38 MAPK, but not GluR2-Ser880, were dependent on hypocretin receptor-1 activation. The intra-accumbens infusion of the protein kinase C (PKC) inhibitor NPC-15437 reduced nicotine-seeking behavior elicited by drug-paired cues consistent with the PKC-dependent phosphorylations of GluR2-Ser880 and NR1-Ser890. SB334867 failed to modify cue-induced reinstatement of food-seeking, which did not produce any biochemical changes in the NAc. These data identify hypocretin receptor-1 and PKC signaling as potential targets for the treatment of relapse to nicotine-seeking induced by nicotine-associated cues.
publishDate 2013
dc.date.none.fl_str_mv 2013
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/23306
http://dx.doi.org/10.1038/npp.2013.72
url http://hdl.handle.net/10230/23306
http://dx.doi.org/10.1038/npp.2013.72
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Neuropsychopharmacology. 2013 Aug;38(9):1724-36
info:eu-repo/grantAgreement/ES/3PN/SAF2011-29864
info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
dc.rights.none.fl_str_mv © Nature Publishing Group. http://dx.doi.org/10.1038/npp.2013.72
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © Nature Publishing Group. http://dx.doi.org/10.1038/npp.2013.72
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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