Plaza-Zabala, Ainhoa, 1982-Martín García, Elena, 1975-Lecea, Luis deMaldonado, Rafael, 1961-Berrendero Díaz, Fernando, 1971-2012-07-052012-07-052010Plaza-Zabala A, Martín-García E, de Lecea L, Maldonado R, Berrendero F. Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior. J Neurosci. 2010;30(6):2300-10. DOI: 10.1523/​JNEUROSCI.5724-09.20100270-6474http://hdl.handle.net/10230/16655Emerging evidence suggests that the hypocretinergic system is involved in addictive behavior. In this study, we investigated the role of these hypothalamic neuropeptides in anxiety-like responses of nicotine and stress-induced reinstatement of nicotine-seeking behavior. Acute nicotine (0.8 mg/kg, s.c.) induced anxiogenic-like effects in the elevated plus-maze and activated the paraventricular nucleus of the/nhypothalamus (PVN) as revealed by c-Fos expression. Pretreatment with the hypocretin receptor 1 (Hcrtr-1) antagonist SB334867 or/npreprohypocretin gene deletion blocked both nicotine effects. In the PVN, SB334867 also prevented the activation of corticotrophin/nreleasing factor (CRF) and arginine-vasopressin (AVP) neurons, which expressed Hcrtr-1. In addition, an increase of the percentage of c-Fos-positive hypocretin cells in the perifornical and dorsomedial hypothalamic (PFA/DMH) areas was found after nicotine (0.8 mg/kg,/ns.c.) administration. Intracerebroventricular infusion of hypocretin-1 (Hcrt-1) (0.75 nmol/1 l) or footshock stress reinstated a previously/nextinguished nicotine-seeking behavior. The effects of Hcrt-1 were blocked by SB334867, but not by the CRF1 receptor antagonist/nantalarmin. Moreover, SB334867 did not block CRF-dependent footshock-induced reinstatement of nicotine-seeking while antalarmin was effective in preventing this nicotine motivational response. Therefore, the Hcrt system interacts with CRF and AVP neurons in the PVN and modulates the anxiogenic-like effects of nicotine whereas Hcrt and CRF play a different role in the reinstatement of nicotineseeking./nIndeed, Hcrt-1 reinstates nicotine-seeking through a mechanism independent of CRF activation whereas CRF mediates the reinstatement induced by stress.application/pdfeng© 2010, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/30/6/2300Nicotina -- AddiccióNicotina -- Efectes fisiològicsinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1523/JNEUROSCI.5724-09.2010info:eu-repo/semantics/openAccess