The hypocretin/orexin system mediates the extinction of fear memories
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- dc.contributor.author Flores de los Heros, África, 1985-ca
- dc.contributor.author Valls Comamala, Victòria, 1987-ca
- dc.contributor.author Costa, Giuliaca
- dc.contributor.author Saravia Santos, Rocio, 1988-ca
- dc.contributor.author Maldonado, Rafael, 1961-ca
- dc.contributor.author Berrendero Díaz, Fernando, 1971-ca
- dc.date.accessioned 2016-01-22T07:54:51Z
- dc.date.available 2016-01-22T07:54:51Z
- dc.date.issued 2014ca
- 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/pdfca
- 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.2014.146ca
- dc.identifier.doi http://dx.doi.org/10.1038/npp.2014.146
- dc.identifier.issn 0893-133Xca
- dc.identifier.uri http://hdl.handle.net/10230/25633
- dc.language.iso engca
- dc.publisher Nature Publishing Groupca
- dc.relation.ispartof Neuropsychopharmacology. 2014 Nov;39(12):2732-41
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29864
- dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/npp.2014.146ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- 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 memoriesca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/acceptedVersionca