Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents

Autores
Laino, Carlos Horacio; Garcia, Pilar Teresa; Podestá, María Fernanda; Höcht, Christian; Slobodianik, Nora Haydee; Reines, Analia Gabriela
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies.
Instituto de Tecnología de Alimentos
Fil: Laino, Carlos Horacio. Universidad Nacional de la Rioja. Centro de Investigación e Innovación Tecnológica. Instituto de Biotecnología; Argentina.
Fil: Garcia, Pilar Teresa. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; Argentina
Fil: Podestá, María Fernanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina.
Fil: Slobodianik, Nora Haydee. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Cátedra de Nutrición; Argentina
Fil: Reines, Analia Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fuente
Journal of Pharmaceutical Sciences 103 (10) : 3316-3325 (October 2014)
Materia
Acidos Grasos
Farmacocinética
Roedores
Fatty Acids
Pharmacokinetics
Rodents
Fluoxetine
Omega-3
Efectos Antidepresivos
Nivel de accesibilidad
acceso restringido
Condiciones de uso
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
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spelling Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodentsLaino, Carlos HoracioGarcia, Pilar TeresaPodestá, María FernandaHöcht, ChristianSlobodianik, Nora HaydeeReines, Analia GabrielaAcidos GrasosFarmacocinéticaRoedoresFatty AcidsPharmacokineticsRodentsFluoxetineOmega-3Efectos AntidepresivosWe previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies.Instituto de Tecnología de AlimentosFil: Laino, Carlos Horacio. Universidad Nacional de la Rioja. Centro de Investigación e Innovación Tecnológica. Instituto de Biotecnología; Argentina.Fil: Garcia, Pilar Teresa. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Podestá, María Fernanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina.Fil: Slobodianik, Nora Haydee. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Cátedra de Nutrición; ArgentinaFil: Reines, Analia Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina2018-08-06T15:44:53Z2018-08-06T15:44:53Z2014-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://www.sciencedirect.com/science/article/pii/S0022354915304020http://hdl.handle.net/20.500.12123/29850022-35491520-6017https://doi.org/10.1002/jps.24123Journal of Pharmaceutical Sciences 103 (10) : 3316-3325 (October 2014)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccess2025-09-29T13:44:23Zoai:localhost:20.500.12123/2985instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-29 13:44:23.792INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents
title Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents
spellingShingle Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents
Laino, Carlos Horacio
Acidos Grasos
Farmacocinética
Roedores
Fatty Acids
Pharmacokinetics
Rodents
Fluoxetine
Omega-3
Efectos Antidepresivos
title_short Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents
title_full Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents
title_fullStr Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents
title_full_unstemmed Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents
title_sort Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents
dc.creator.none.fl_str_mv Laino, Carlos Horacio
Garcia, Pilar Teresa
Podestá, María Fernanda
Höcht, Christian
Slobodianik, Nora Haydee
Reines, Analia Gabriela
author Laino, Carlos Horacio
author_facet Laino, Carlos Horacio
Garcia, Pilar Teresa
Podestá, María Fernanda
Höcht, Christian
Slobodianik, Nora Haydee
Reines, Analia Gabriela
author_role author
author2 Garcia, Pilar Teresa
Podestá, María Fernanda
Höcht, Christian
Slobodianik, Nora Haydee
Reines, Analia Gabriela
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Acidos Grasos
Farmacocinética
Roedores
Fatty Acids
Pharmacokinetics
Rodents
Fluoxetine
Omega-3
Efectos Antidepresivos
topic Acidos Grasos
Farmacocinética
Roedores
Fatty Acids
Pharmacokinetics
Rodents
Fluoxetine
Omega-3
Efectos Antidepresivos
dc.description.none.fl_txt_mv We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies.
Instituto de Tecnología de Alimentos
Fil: Laino, Carlos Horacio. Universidad Nacional de la Rioja. Centro de Investigación e Innovación Tecnológica. Instituto de Biotecnología; Argentina.
Fil: Garcia, Pilar Teresa. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; Argentina
Fil: Podestá, María Fernanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina.
Fil: Slobodianik, Nora Haydee. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Cátedra de Nutrición; Argentina
Fil: Reines, Analia Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
description We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies.
publishDate 2014
dc.date.none.fl_str_mv 2014-10
2018-08-06T15:44:53Z
2018-08-06T15:44:53Z
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S0022354915304020
http://hdl.handle.net/20.500.12123/2985
0022-3549
1520-6017
https://doi.org/10.1002/jps.24123
url https://www.sciencedirect.com/science/article/pii/S0022354915304020
http://hdl.handle.net/20.500.12123/2985
https://doi.org/10.1002/jps.24123
identifier_str_mv 0022-3549
1520-6017
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
eu_rights_str_mv restrictedAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Journal of Pharmaceutical Sciences 103 (10) : 3316-3325 (October 2014)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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score 12.559606

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