Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/53410 |
Resumo: | © 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/). |
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Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behaviorAdolescenceAnxietyCannabinoidsDepressionHU-210Stress© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/).Chronic adolescent cannabinoid receptor agonist exposure has been shown to lead to persistent increases in depressive-like behaviors. This has been a key obstacle to the development of cannabinoid-based therapeutics. However, most of the published work has been performed with only three compounds, namely Δ9-tetrahydrocannabinol, CP55,940 and WIN55,212-2. Hypothesizing that different compounds may lead to distinct outcomes, we herein used the highly potent CB1R/CB2R full agonist HU-210, and first aimed at replicating cannabinoid-induced long-lasting effects, by exposing adolescent female Sprague-Dawley rats to increasing doses of HU-210, for 11 days and testing them at adulthood, after a 30-day drug washout. Surprisingly, HU-210 did not significantly impact adult anxious- or depressive-like behaviors. We then tested whether chronic adolescent HU-210 treatment resulted in short-term (24h) alterations in depressive-like behavior. Remarkably, HU-210 treatment simultaneously induced marked antidepressant- and prodepressant-like responses, in the modified forced swim (mFST) and sucrose preference tests (SPT), respectively. Hypothesizing that mFST results were a misleading artifact of HU-210-induced behavioral hyperreactivity to stress, we assessed plasmatic noradrenaline and corticosterone levels, under basal conditions and following an acute swim-stress episode. Notably, we found that while HU-210 did not alter basal noradrenaline or corticosterone levels, it greatly augmented the stress-induced increase in both. Our results show that, contrary to previously studied cannabinoid receptor agonists, HU-210 does not induce persisting depressive-like alterations, despite inducing marked short-term increases in stress-induced reactivity. By showing that not all cannabinoid receptor agonists may induce long-term negative effects, these results hold significant relevance for the development of cannabinoid-based therapeutics.Work was supported by project funding from Fundação para a Ciência e para a Tecnologia (FCT) (PTDC/MED-FAR/30933/2017 and PTDC/MED-FAR/4834/2021) and by H2020-WIDESPREAD-05-2017-Twinning (EpiEpinet) under grant agreement No. 952455. MF-F (SFRH/BD/147505/2019), NR (PD/BD/113463/2015), JF-G (PD/BD/114441/2016) and CM-L (SFRH/BD/118238/2016) are supported by PhD fellowships from FCT. The funding sources had no involvement in study design, preparation of the manuscript, or decision regarding its submission.ElsevierRepositório da Universidade de LisboaFarinha Ferreira, Jorge MiguelRei, NádiaFonseca-Gomes, JoãoMiranda-Lourenço, CatarinaSerrão, PaulaVaz, Sandra H.Gomes, Joana I.Martins, ValériaPereira, Beatriz de AlvesSebastião, Ana M2022-06-20T15:17:09Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53410engNeuropharmacology. 2022 Aug 15;214:1091550028-390810.1016/j.neuropharm.2022.1091551873-7064info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:59:09Zoai:repositorio.ul.pt:10451/53410Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:21.497496Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior |
| title |
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior |
| spellingShingle |
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior Farinha Ferreira, Jorge Miguel Adolescence Anxiety Cannabinoids Depression HU-210 Stress |
| title_short |
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior |
| title_full |
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior |
| title_fullStr |
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior |
| title_full_unstemmed |
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior |
| title_sort |
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior |
| author |
Farinha Ferreira, Jorge Miguel |
| author_facet |
Farinha Ferreira, Jorge Miguel Rei, Nádia Fonseca-Gomes, João Miranda-Lourenço, Catarina Serrão, Paula Vaz, Sandra H. Gomes, Joana I. Martins, Valéria Pereira, Beatriz de Alves Sebastião, Ana M |
| author_role |
author |
| author2 |
Rei, Nádia Fonseca-Gomes, João Miranda-Lourenço, Catarina Serrão, Paula Vaz, Sandra H. Gomes, Joana I. Martins, Valéria Pereira, Beatriz de Alves Sebastião, Ana M |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Farinha Ferreira, Jorge Miguel Rei, Nádia Fonseca-Gomes, João Miranda-Lourenço, Catarina Serrão, Paula Vaz, Sandra H. Gomes, Joana I. Martins, Valéria Pereira, Beatriz de Alves Sebastião, Ana M |
| dc.subject.por.fl_str_mv |
Adolescence Anxiety Cannabinoids Depression HU-210 Stress |
| topic |
Adolescence Anxiety Cannabinoids Depression HU-210 Stress |
| description |
© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/). |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-06-20T15:17:09Z 2022 2022-01-01T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/53410 |
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http://hdl.handle.net/10451/53410 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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Neuropharmacology. 2022 Aug 15;214:109155 0028-3908 10.1016/j.neuropharm.2022.109155 1873-7064 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Elsevier |
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Elsevier |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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