The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling
Autor(a) principal: | |
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Data de Publicação: | 2009 |
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/1822/64291 |
Resumo: | The mechanisms underlying the initiation/onset of, and the recovery from, depression are still largely unknown; views that neurogenesis in the hippocampus may be important for the pathogenesis and amelioration of depressive symptoms have gained currency over the years although the original evidence has been challenged. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 2 weeks of stress exposure, animals were treated with the antidepressants fluoxetine, imipramine, CP 156,526 or SSR 1494515, alone or combined with methylazoxymethanol, a cytostatic agent used to arrest neurogenesis. We found that antidepressants retain their therapeutic efficacy in reducing both measured indices of depression-like behavior (learned helplessness and anhedonia), even when neurogenesis is blocked. Instead, our experiments suggest re-establishment of neuronal plasticity (dendritic remodeling and synaptic contacts) in the hippocampus and prefrontal cortex, rather than neurogenesis, as the basis for the restoration of behavioral homeostasis by antidepressants. |
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The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodelingAffectAnalysis of VarianceAnimalsAntidepressive AgentsAntidiuretic Hormone Receptor AntagonistsBehavior, AnimalCytostatic AgentsDepressionDrug CombinationsFluoxetineHippocampusImipramineIndolesMaleMethylazoxymethanol AcetateMitosisNeurogenesisNeuronal PlasticityPrefrontal CortexPyrrolidinesRatsRats, WistarReceptors, Corticotropin-Releasing HormoneStress, PsychologicalneuroplasticityantidepressantNCAMsynapsin 1Science & TechnologyThe mechanisms underlying the initiation/onset of, and the recovery from, depression are still largely unknown; views that neurogenesis in the hippocampus may be important for the pathogenesis and amelioration of depressive symptoms have gained currency over the years although the original evidence has been challenged. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 2 weeks of stress exposure, animals were treated with the antidepressants fluoxetine, imipramine, CP 156,526 or SSR 1494515, alone or combined with methylazoxymethanol, a cytostatic agent used to arrest neurogenesis. We found that antidepressants retain their therapeutic efficacy in reducing both measured indices of depression-like behavior (learned helplessness and anhedonia), even when neurogenesis is blocked. Instead, our experiments suggest re-establishment of neuronal plasticity (dendritic remodeling and synaptic contacts) in the hippocampus and prefrontal cortex, rather than neurogenesis, as the basis for the restoration of behavioral homeostasis by antidepressants.This project used compound(s) provided by the National Cancer Institute’s Chemical Carcinogen Reference Standards Repository (operated under contract N02-CB-07008 by Midwest Research Institute; MAM), Sanofi-Synthelabo (SSR 149415) and Pfizer (CP 156,526). The authors’ work was supported by the Portuguese Foundation for Science and Technology (FCT) (PTDC/SAU-NEU/72699/2006).Nature Publishing GroupUniversidade do MinhoBessa, J. M.Ferreira, D.Melo, I.Marques, F.Cerqueira, João JoséPalha, Joana AlmeidaAlmeida, O. F. X.Sousa, Nuno2009-082009-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/64291eng1359-418410.1038/mp.2008.1191476-557818982002info: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:RCAAP2023-07-21T12:27:59Zoai:repositorium.sdum.uminho.pt:1822/64291Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:22:42.177782Repositório 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 |
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling |
title |
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling |
spellingShingle |
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling Bessa, J. M. Affect Analysis of Variance Animals Antidepressive Agents Antidiuretic Hormone Receptor Antagonists Behavior, Animal Cytostatic Agents Depression Drug Combinations Fluoxetine Hippocampus Imipramine Indoles Male Methylazoxymethanol Acetate Mitosis Neurogenesis Neuronal Plasticity Prefrontal Cortex Pyrrolidines Rats Rats, Wistar Receptors, Corticotropin-Releasing Hormone Stress, Psychological neuroplasticity antidepressant NCAM synapsin 1 Science & Technology |
title_short |
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling |
title_full |
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling |
title_fullStr |
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling |
title_full_unstemmed |
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling |
title_sort |
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling |
author |
Bessa, J. M. |
author_facet |
Bessa, J. M. Ferreira, D. Melo, I. Marques, F. Cerqueira, João José Palha, Joana Almeida Almeida, O. F. X. Sousa, Nuno |
author_role |
author |
author2 |
Ferreira, D. Melo, I. Marques, F. Cerqueira, João José Palha, Joana Almeida Almeida, O. F. X. Sousa, Nuno |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Bessa, J. M. Ferreira, D. Melo, I. Marques, F. Cerqueira, João José Palha, Joana Almeida Almeida, O. F. X. Sousa, Nuno |
dc.subject.por.fl_str_mv |
Affect Analysis of Variance Animals Antidepressive Agents Antidiuretic Hormone Receptor Antagonists Behavior, Animal Cytostatic Agents Depression Drug Combinations Fluoxetine Hippocampus Imipramine Indoles Male Methylazoxymethanol Acetate Mitosis Neurogenesis Neuronal Plasticity Prefrontal Cortex Pyrrolidines Rats Rats, Wistar Receptors, Corticotropin-Releasing Hormone Stress, Psychological neuroplasticity antidepressant NCAM synapsin 1 Science & Technology |
topic |
Affect Analysis of Variance Animals Antidepressive Agents Antidiuretic Hormone Receptor Antagonists Behavior, Animal Cytostatic Agents Depression Drug Combinations Fluoxetine Hippocampus Imipramine Indoles Male Methylazoxymethanol Acetate Mitosis Neurogenesis Neuronal Plasticity Prefrontal Cortex Pyrrolidines Rats Rats, Wistar Receptors, Corticotropin-Releasing Hormone Stress, Psychological neuroplasticity antidepressant NCAM synapsin 1 Science & Technology |
description |
The mechanisms underlying the initiation/onset of, and the recovery from, depression are still largely unknown; views that neurogenesis in the hippocampus may be important for the pathogenesis and amelioration of depressive symptoms have gained currency over the years although the original evidence has been challenged. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 2 weeks of stress exposure, animals were treated with the antidepressants fluoxetine, imipramine, CP 156,526 or SSR 1494515, alone or combined with methylazoxymethanol, a cytostatic agent used to arrest neurogenesis. We found that antidepressants retain their therapeutic efficacy in reducing both measured indices of depression-like behavior (learned helplessness and anhedonia), even when neurogenesis is blocked. Instead, our experiments suggest re-establishment of neuronal plasticity (dendritic remodeling and synaptic contacts) in the hippocampus and prefrontal cortex, rather than neurogenesis, as the basis for the restoration of behavioral homeostasis by antidepressants. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-08 2009-08-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/64291 |
url |
http://hdl.handle.net/1822/64291 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1359-4184 10.1038/mp.2008.119 1476-5578 18982002 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
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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