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The hypocretin/orexin system mediates the extinction of fear memories

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dc.contributor.author Flores de los Heros, África, 1985-
dc.contributor.author Valls Comamala, Victòria, 1987-
dc.contributor.author Costa, Giulia
dc.contributor.author Saravia Santos, Rocio, 1988-
dc.contributor.author Maldonado, Rafael, 1961-
dc.contributor.author Berrendero Díaz, Fernando, 1971-
dc.date.accessioned 2016-01-22T07:54:51Z
dc.date.available 2016-01-22T07:54:51Z
dc.date.issued 2014
dc.identifier.citation Flores Á, Valls-Comamala V, Costa G, Saravia R, Maldonado R, Berrendero F. The hypocretin/orexin system mediates the extinction of fear memories. Neuropsychopharmacology. 2014 Nov;39(12):2732-41. DOI: 10.1038/npp.2014.146
dc.identifier.issn 0893-133X
dc.identifier.uri http://hdl.handle.net/10230/25633
dc.description.abstract Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear conditioning and extinction. Hypocretins were crucial for the consolidation of fear conditioning, and this effect was mainly observed in memories with a high emotional component. Notably, after the acquisition of fear memory, hypocretin receptor-1 blockade facilitated fear extinction, whereas hypocretin-1 administration impaired this extinction process. The extinction-facilitating effects of the hypocretin receptor-1 antagonist SB334867 were associated with increased expression of cFos in the basolateral amygdala and the infralimbic cortex. Intra-amygdala, but neither intra-infralimbic prefrontal cortex nor intra-dorsohippocampal infusion of SB334867 enhanced fear extinction. These results reveal a key role for hypocretins in the extinction of aversive memories and suggest that hypocretin receptor-1 blockade could represent a novel therapeutic target for the treatment of diseases associated with inappropriate retention of fear, such as post-traumatic stress disorder and phobias.
dc.description.sponsorship This work was supported by the Instituto de Salud Carlos III grants, #PI13/00042 and #RD12/0028/0023 (RTA-RETICS), by the Spanish Ministry of Science #SAF2011-29864, the/nCatalan Government (SGR2009-00731), and by the Catalan Institution for Research and Advanced Studies (ICREA Academia program). África Flores is a recipient of a predoctoral fellowship from the Spanish Ministry of Education.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.ispartof Neuropsychopharmacology. 2014 Nov;39(12):2732-41
dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/npp.2014.146
dc.subject.other Extinció psicològica
dc.subject.other Por -- Aspectes fisiològics
dc.subject.other Pèptids
dc.subject.other Memòria -- Aspectes fisiològics
dc.title The hypocretin/orexin system mediates the extinction of fear memories
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/npp.2014.146
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29864
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion


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