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

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....

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Detalles Bibliográficos
Autores: Plaza-Zabala, Ainhoa, 1982-, Martín García, Elena, 1975-, Lecea, Luis de, Maldonado, Rafael, 1961-, Berrendero Díaz, Fernando, 1971-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
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:10230/16655
Acceso en línea:http://hdl.handle.net/10230/16655
http://dx.doi.org/10.1523/JNEUROSCI.5724-09.2010
Access Level:acceso abierto
Palabra clave:Nicotina -- Addicció
Nicotina -- Efectes fisiològics
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spelling Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behaviorPlaza-Zabala, Ainhoa, 1982-Martín García, Elena, 1975-Lecea, Luis deMaldonado, Rafael, 1961-Berrendero Díaz, Fernando, 1971-Nicotina -- AddiccióNicotina -- Efectes fisiològicsEmerging 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.This work was supported by the Instituto de Salud Carlos III Grants PI070559 (FIS) and RD06/001/001 (RTA-RETICS), by the Spanish Ministry of Science and Technology (Consolider-C, SAF2007-64062), by the European Commission (IP LSHM-CT-2004-05166, GENADDICT; and STREP LHSM-CT-2007-037669, PHECOMP), by the Catalan Institution for Research and Advanced Studies (ICREA Academia program), and by Generalitat de Catalunya (2009SGR00731). L.d.L. is supported by grants from the National Institute on Drug Abuse, National Alliance for Research on Schizophrenia and Depression, and Defense Advanced Research Projects Agency.E.M.-G.was supported by a postdoctoral fellowship from the Spanish Instituto de Salud Carlos III. A.P.-Z. is a recipient of a predoctoral fellowship from the Spanish Ministry of Education. We thank R. Cabrera, M. Linares, T. Hansson, and C. Fernández-Avilés for invaluable technical assistance, and T. Sakurai and M. Yanagisawa for generously providing preprohypocretin knock-out miceSociety for Neuroscience201220122010info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/16655http://dx.doi.org/10.1523/JNEUROSCI.5724-09.2010reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésJournal of Neuroscience. 2010;30(6):2300-10info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062© 2010, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/30/6/2300info:eu-repo/semantics/openAccessoai:recercat.cat:10230/166552026-05-29T05:05:01Z
dc.title.none.fl_str_mv Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior
title Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior
spellingShingle Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior
Plaza-Zabala, Ainhoa, 1982-
Nicotina -- Addicció
Nicotina -- Efectes fisiològics
title_short Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior
title_full Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior
title_fullStr Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior
title_full_unstemmed Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior
title_sort Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior
dc.creator.none.fl_str_mv Plaza-Zabala, Ainhoa, 1982-
Martín García, Elena, 1975-
Lecea, Luis de
Maldonado, Rafael, 1961-
Berrendero Díaz, Fernando, 1971-
author Plaza-Zabala, Ainhoa, 1982-
author_facet Plaza-Zabala, Ainhoa, 1982-
Martín García, Elena, 1975-
Lecea, Luis de
Maldonado, Rafael, 1961-
Berrendero Díaz, Fernando, 1971-
author_role author
author2 Martín García, Elena, 1975-
Lecea, Luis de
Maldonado, Rafael, 1961-
Berrendero Díaz, Fernando, 1971-
author2_role author
author
author
author
dc.subject.none.fl_str_mv Nicotina -- Addicció
Nicotina -- Efectes fisiològics
topic Nicotina -- Addicció
Nicotina -- Efectes fisiològics
description 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/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.
publishDate 2010
dc.date.none.fl_str_mv 2010
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/16655
http://dx.doi.org/10.1523/JNEUROSCI.5724-09.2010
url http://hdl.handle.net/10230/16655
http://dx.doi.org/10.1523/JNEUROSCI.5724-09.2010
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Neuroscience. 2010;30(6):2300-10
info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
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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