Plaza-Zabala, Ainhoa, 1982-Flores de los Heros, África, 1985-Martín García, Elena, 1975-Saravia Santos, Rocio, 1988-Maldonado, Rafael, 1961-Berrendero Díaz, Fernando, 1971-2015-03-302015-03-302013Plaza-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.2013.720893-133Xhttp://hdl.handle.net/10230/23306Hypocretin/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.application/pdfeng© Nature Publishing Group. http://dx.doi.org/10.1038/npp.2013.72Nicotina -- AddiccióNicotina -- Farmacologiainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/npp.2013.72info:eu-repo/semantics/openAccess