A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior
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- dc.contributor.author Plaza-Zabala, Ainhoa, 1982-ca
- dc.contributor.author Flores de los Heros, África, 1985-ca
- dc.contributor.author Martín García, Elena, 1975-ca
- dc.contributor.author Saravia Santos, Rocio, 1988-ca
- dc.contributor.author Maldonado, Rafael, 1961-ca
- dc.contributor.author Berrendero Díaz, Fernando, 1971-ca
- dc.date.accessioned 2015-03-30T07:21:10Z
- dc.date.available 2015-03-30T07:21:10Z
- dc.date.issued 2013ca
- dc.description.abstract 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.
- dc.description.sponsorship 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 Education
- dc.format.mimetype application/pdfca
- dc.identifier.citation Plaza-Zabala A, Flores Á, Martín-García E, Saravia R, Maldonado R, Berrendero F. A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior. Neuropsychopharmacology. 2013 Aug;38(9):1724-36. DOI: 10.1038/npp.2013.72ca
- dc.identifier.doi http://dx.doi.org/10.1038/npp.2013.72
- dc.identifier.issn 0893-133Xca
- dc.identifier.uri http://hdl.handle.net/10230/23306
- dc.language.iso engca
- dc.publisher Nature Publishing Groupca
- dc.relation.ispartof Neuropsychopharmacology. 2013 Aug;38(9):1724-36
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29864
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
- dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/npp.2013.72ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Nicotina -- Addicció
- dc.subject.other Nicotina -- Farmacologia
- dc.title A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behaviorca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/acceptedVersionca