Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior

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Plaza-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.5724-09.2010
http://hdl.handle.net/10230/16655
To cite or link this document: http://hdl.handle.net/10230/16655
dc.contributor.author Plaza Zabala, Ainhoa
dc.contributor.author Martín García, Elena
dc.contributor.author Lecea, Luis de
dc.contributor.author Maldonado, Rafael
dc.contributor.author Berrendero Díaz, Fernando
dc.date.accessioned 2012-07-05T06:53:35Z
dc.date.available 2012-07-05T06:53:35Z
dc.date.issued 2010
dc.identifier.citation Plaza-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.5724-09.2010
dc.identifier.issn 0270-6474
dc.identifier.uri http://hdl.handle.net/10230/16655
dc.description.abstract Emerging 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 hypothalamus (PVN) as revealed by c-Fos expression. Pretreatment with the hypocretin receptor 1 (Hcrtr-1) antagonist SB334867 or preprohypocretin gene deletion blocked both nicotine effects. In the PVN, SB334867 also prevented the activation of corticotrophin releasing 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, s.c.) administration. Intracerebroventricular infusion of hypocretin-1 (Hcrt-1) (0.75 nmol/1 l) or footshock stress reinstated a previously extinguished nicotine-seeking behavior. The effects of Hcrt-1 were blocked by SB334867, but not by the CRF1 receptor antagonist antalarmin. 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. Indeed, Hcrt-1 reinstates nicotine-seeking through a mechanism independent of CRF activation whereas CRF mediates the reinstatement induced by stress.
dc.language.iso eng
dc.publisher Society for Neuroscience
dc.relation.ispartof J Neurosci. 2010; 30(6): 2300-10
dc.rights (c) 2010, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/30/6/2300
dc.subject.other Nicotina -- Addicció
dc.subject.other Nicotina -- Efectes fisiològics
dc.title Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1523/JNEUROSCI.5724-09.2010
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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