The hypocretin/orexin system mediates the extinction of fear memories
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 hypocreti...
| Autores: | , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/25633 |
| Acceso en línea: | http://hdl.handle.net/10230/25633 http://dx.doi.org/10.1038/npp.2014.146 |
| Access Level: | acceso abierto |
| Palabra clave: | Extinció psicològica Por -- Aspectes fisiològics Pèptids Memòria -- Aspectes fisiològics |
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The hypocretin/orexin system mediates the extinction of fear memoriesFlores de los Heros, África, 1985-Valls Comamala, Victòria, 1987-Costa, GiuliaSaravia Santos, Rocio, 1988-Maldonado, Rafael, 1961-Berrendero Díaz, Fernando, 1971-Extinció psicològicaPor -- Aspectes fisiològicsPèptidsMemòria -- Aspectes fisiològicsAnxiety 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.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.Nature Publishing Group201620162014info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/25633http://dx.doi.org/10.1038/npp.2014.146reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNeuropsychopharmacology. 2014 Nov;39(12):2732-41info:eu-repo/grantAgreement/ES/3PN/SAF2011-29864© Nature Publishing Group. http://dx.doi.org/10.1038/npp.2014.146info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/256332026-06-12T07:21:37Z |
| dc.title.none.fl_str_mv |
The hypocretin/orexin system mediates the extinction of fear memories |
| title |
The hypocretin/orexin system mediates the extinction of fear memories |
| spellingShingle |
The hypocretin/orexin system mediates the extinction of fear memories Flores de los Heros, África, 1985- Extinció psicològica Por -- Aspectes fisiològics Pèptids Memòria -- Aspectes fisiològics |
| title_short |
The hypocretin/orexin system mediates the extinction of fear memories |
| title_full |
The hypocretin/orexin system mediates the extinction of fear memories |
| title_fullStr |
The hypocretin/orexin system mediates the extinction of fear memories |
| title_full_unstemmed |
The hypocretin/orexin system mediates the extinction of fear memories |
| title_sort |
The hypocretin/orexin system mediates the extinction of fear memories |
| dc.creator.none.fl_str_mv |
Flores de los Heros, África, 1985- Valls Comamala, Victòria, 1987- Costa, Giulia Saravia Santos, Rocio, 1988- Maldonado, Rafael, 1961- Berrendero Díaz, Fernando, 1971- |
| author |
Flores de los Heros, África, 1985- |
| author_facet |
Flores de los Heros, África, 1985- Valls Comamala, Victòria, 1987- Costa, Giulia Saravia Santos, Rocio, 1988- Maldonado, Rafael, 1961- Berrendero Díaz, Fernando, 1971- |
| author_role |
author |
| author2 |
Valls Comamala, Victòria, 1987- Costa, Giulia Saravia Santos, Rocio, 1988- Maldonado, Rafael, 1961- Berrendero Díaz, Fernando, 1971- |
| author2_role |
author author author author author |
| dc.subject.none.fl_str_mv |
Extinció psicològica Por -- Aspectes fisiològics Pèptids Memòria -- Aspectes fisiològics |
| topic |
Extinció psicològica Por -- Aspectes fisiològics Pèptids Memòria -- Aspectes fisiològics |
| description |
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. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014 2016 2016 |
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info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
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article |
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acceptedVersion |
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http://hdl.handle.net/10230/25633 http://dx.doi.org/10.1038/npp.2014.146 |
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http://hdl.handle.net/10230/25633 http://dx.doi.org/10.1038/npp.2014.146 |
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Inglés |
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Inglés |
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Neuropsychopharmacology. 2014 Nov;39(12):2732-41 info:eu-repo/grantAgreement/ES/3PN/SAF2011-29864 |
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© Nature Publishing Group. http://dx.doi.org/10.1038/npp.2014.146 info:eu-repo/semantics/openAccess |
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© Nature Publishing Group. http://dx.doi.org/10.1038/npp.2014.146 |
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openAccess |
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Nature Publishing Group |
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Nature Publishing Group |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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Universitat Pompeu Fabra |
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