Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood
Δ9-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behaviou...
| Autores: | , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versión aceptada para publicación |
| Data de publicação: | 2019 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositório: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/36268 |
| Acesso em linha: | http://hdl.handle.net/10230/36268 http://dx.doi.org/10.1016/j.neuropharm.2018.11.016 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Adolescència Nucli amigdaloide Espina dendrítica Por Estrès Tetrahidrocannabinol |
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Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthoodSaravia Santos, Rocio, 1988-Ten-Blanco, MarcJulià Hernández, MarinaGagliano, HumbertoAndero, RaülArmario García, AntonioMaldonado, Rafael, 1961-Berrendero Díaz, Fernando, 1971-AdolescènciaNucli amigdaloideEspina dendríticaPorEstrèsTetrahidrocannabinolΔ9-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behavioural deficits in adulthood. Here we investigate the effects of THC treatment as well as the consequences of concomitant THC and stress exposure during adolescence in the extinction of fear memory in adult mice. Adolescent mice treated with THC and exposed to stress exhibit impaired cued fear extinction in adulthood. However, no effect was observed in animals exposed to these two factors separately. Notably, resistance to fear extinction was associated with decreased neuronal activity in the basolateral amygdala (BLA) and the infralimbic prefrontal cortex, suggesting a long-term dysregulation of the fear circuit. These changes in neuronal activation were paralleled with structural plasticity alterations. Indeed, an increase of immature dendritic spines in pyramidal neurons of the BLA was revealed in mice simultaneously exposed to THC and stress. Corticosterone levels were also enhanced after the cued fear conditioning session in the same experimental group. These results show that an interaction between cannabis exposure and stress during adolescence may lead to long-term anxiety disorders characterized by the presence of pathological fear.This work was supported by “Plan Nacional sobre Drogas” (#2014I019) and “Ministerio de Economía y Competitividad” (SAF2017-85299-R) to FB, the "Generalitat de Catalunya-AGAUR" (#2014-SGR-1547), ICREA-Acadèmia(2015) and “Ministerio de Economía y Competitividad” (#SAF2017-84060-R) to RM, NARSAD Young Investigator Grant #22434, Ramón y Cajal program RYC2014-15784, RETOS-MINECOSAF2016-76565-R and FEDER funds to RA, and “Ministerio de Economía y Competitividad” (SAF2014-53876R) and “Generalitat de Catalunya” (SGR 2014-1020) to AAElsevier20192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/36268http://dx.doi.org/10.1016/j.neuropharm.2018.11.016reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNeuropharmacology. 2019 Jan;144:345-57info:eu-repo/grantAgreement/ES/1PE/SAF2017-85299-Rinfo:eu-repo/grantAgreement/ES/1PE/SAF2017-84060-Rinfo:eu-repo/grantAgreement/ES/1PE/SAF2016-76565-Rinfo:eu-repo/grantAgreement/ES/1PE/SAF2014-53876R© Elsevier http://dx.doi.org/10.1016/j.neuropharm.2018.11.016info:eu-repo/semantics/openAccessoai:recercat.cat:10230/362682026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood |
| title |
Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood |
| spellingShingle |
Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood Saravia Santos, Rocio, 1988- Adolescència Nucli amigdaloide Espina dendrítica Por Estrès Tetrahidrocannabinol |
| title_short |
Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood |
| title_full |
Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood |
| title_fullStr |
Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood |
| title_full_unstemmed |
Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood |
| title_sort |
Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood |
| dc.creator.none.fl_str_mv |
Saravia Santos, Rocio, 1988- Ten-Blanco, Marc Julià Hernández, Marina Gagliano, Humberto Andero, Raül Armario García, Antonio Maldonado, Rafael, 1961- Berrendero Díaz, Fernando, 1971- |
| author |
Saravia Santos, Rocio, 1988- |
| author_facet |
Saravia Santos, Rocio, 1988- Ten-Blanco, Marc Julià Hernández, Marina Gagliano, Humberto Andero, Raül Armario García, Antonio Maldonado, Rafael, 1961- Berrendero Díaz, Fernando, 1971- |
| author_role |
author |
| author2 |
Ten-Blanco, Marc Julià Hernández, Marina Gagliano, Humberto Andero, Raül Armario García, Antonio Maldonado, Rafael, 1961- Berrendero Díaz, Fernando, 1971- |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
Adolescència Nucli amigdaloide Espina dendrítica Por Estrès Tetrahidrocannabinol |
| topic |
Adolescència Nucli amigdaloide Espina dendrítica Por Estrès Tetrahidrocannabinol |
| description |
Δ9-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behavioural deficits in adulthood. Here we investigate the effects of THC treatment as well as the consequences of concomitant THC and stress exposure during adolescence in the extinction of fear memory in adult mice. Adolescent mice treated with THC and exposed to stress exhibit impaired cued fear extinction in adulthood. However, no effect was observed in animals exposed to these two factors separately. Notably, resistance to fear extinction was associated with decreased neuronal activity in the basolateral amygdala (BLA) and the infralimbic prefrontal cortex, suggesting a long-term dysregulation of the fear circuit. These changes in neuronal activation were paralleled with structural plasticity alterations. Indeed, an increase of immature dendritic spines in pyramidal neurons of the BLA was revealed in mice simultaneously exposed to THC and stress. Corticosterone levels were also enhanced after the cued fear conditioning session in the same experimental group. These results show that an interaction between cannabis exposure and stress during adolescence may lead to long-term anxiety disorders characterized by the presence of pathological fear. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
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article |
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acceptedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/36268 http://dx.doi.org/10.1016/j.neuropharm.2018.11.016 |
| url |
http://hdl.handle.net/10230/36268 http://dx.doi.org/10.1016/j.neuropharm.2018.11.016 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Neuropharmacology. 2019 Jan;144:345-57 info:eu-repo/grantAgreement/ES/1PE/SAF2017-85299-R info:eu-repo/grantAgreement/ES/1PE/SAF2017-84060-R info:eu-repo/grantAgreement/ES/1PE/SAF2016-76565-R info:eu-repo/grantAgreement/ES/1PE/SAF2014-53876R |
| dc.rights.none.fl_str_mv |
© Elsevier http://dx.doi.org/10.1016/j.neuropharm.2018.11.016 info:eu-repo/semantics/openAccess |
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© Elsevier http://dx.doi.org/10.1016/j.neuropharm.2018.11.016 |
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openAccess |
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application/pdf application/pdf |
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Elsevier |
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Elsevier |
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reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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