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/10362/151392 |
Resumo: | Funding Information: 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. Publisher Copyright: © 2022 |
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Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behaviorAdolescenceAnxietyCannabinoidsDepressionHU-210StressPharmacologyCellular and Molecular NeuroscienceFunding Information: 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. Publisher Copyright: © 2022Chronic 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.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNFarinha-Ferreira, MiguelRei, NádiaFonseca-Gomes, JoãoMiranda-Lourenço, CatarinaSerrão, PaulaVaz, Sandra H.Gomes, Joana I.Martins, Valériade Alves Pereira, BeatrizSebastião, Ana M.2023-03-29T22:22:38Z2022-08-152022-08-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/151392eng0028-3908PURE: 57246873https://doi.org/10.1016/j.neuropharm.2022.109155info: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:RCAAP2024-03-11T05:33:50Zoai:run.unl.pt:10362/151392Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:54:34.361020Repositório 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, Miguel Adolescence Anxiety Cannabinoids Depression HU-210 Stress Pharmacology Cellular and Molecular Neuroscience |
| 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, Miguel |
| author_facet |
Farinha-Ferreira, Miguel Rei, Nádia Fonseca-Gomes, João Miranda-Lourenço, Catarina Serrão, Paula Vaz, Sandra H. Gomes, Joana I. Martins, Valéria de Alves Pereira, Beatriz 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 de Alves Pereira, Beatriz Sebastião, Ana M. |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
| dc.contributor.author.fl_str_mv |
Farinha-Ferreira, Miguel Rei, Nádia Fonseca-Gomes, João Miranda-Lourenço, Catarina Serrão, Paula Vaz, Sandra H. Gomes, Joana I. Martins, Valéria de Alves Pereira, Beatriz Sebastião, Ana M. |
| dc.subject.por.fl_str_mv |
Adolescence Anxiety Cannabinoids Depression HU-210 Stress Pharmacology Cellular and Molecular Neuroscience |
| topic |
Adolescence Anxiety Cannabinoids Depression HU-210 Stress Pharmacology Cellular and Molecular Neuroscience |
| description |
Funding Information: 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. Publisher Copyright: © 2022 |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-08-15 2022-08-15T00:00:00Z 2023-03-29T22:22:38Z |
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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 |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/151392 |
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http://hdl.handle.net/10362/151392 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
0028-3908 PURE: 57246873 https://doi.org/10.1016/j.neuropharm.2022.109155 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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