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

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 omeg...

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Main Authors: Laino, Carlos Horacio, Garcia, Pilar Teresa, Podestá, María Fernanda, Höcht, Christian, Slobodianik, Nora Haydee, Reines, Analia Gabriela
Format: info:ar-repo/semantics/artículo
Language:Inglés
Published: 2018
Subjects:
Online Access:https://www.sciencedirect.com/science/article/pii/S0022354915304020
http://hdl.handle.net/20.500.12123/2985
https://doi.org/10.1002/jps.24123
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author Laino, Carlos Horacio
Garcia, Pilar Teresa
Podestá, María Fernanda
Höcht, Christian
Slobodianik, Nora Haydee
Reines, Analia Gabriela
author_browse Garcia, Pilar Teresa
Höcht, Christian
Laino, Carlos Horacio
Podestá, María Fernanda
Reines, Analia Gabriela
Slobodianik, Nora Haydee
author_facet Laino, Carlos Horacio
Garcia, Pilar Teresa
Podestá, María Fernanda
Höcht, Christian
Slobodianik, Nora Haydee
Reines, Analia Gabriela
author_sort Laino, Carlos Horacio
collection INTA Digital
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.
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institution Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina)
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spelling INTA29852018-08-06T15:46:19Z Fluoxetine potentiation of Omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents Laino, Carlos Horacio Garcia, Pilar Teresa Podestá, María Fernanda Höcht, Christian Slobodianik, Nora Haydee Reines, Analia Gabriela Acidos Grasos Farmacocinética Roedores Fatty Acids Pharmacokinetics Rodents Fluoxetine Omega-3 Efectos Antidepresivos 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 2018-08-06T15:44:53Z 2018-08-06T15:44:53Z 2014-10 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng info:eu-repo/semantics/restrictedAccess application/pdf Journal of Pharmaceutical Sciences 103 (10) : 3316-3325 (October 2014)
spellingShingle Acidos Grasos
Farmacocinética
Roedores
Fatty Acids
Pharmacokinetics
Rodents
Fluoxetine
Omega-3
Efectos Antidepresivos
Laino, Carlos Horacio
Garcia, Pilar Teresa
Podestá, María Fernanda
Höcht, Christian
Slobodianik, Nora Haydee
Reines, Analia Gabriela
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
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_short 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
topic Acidos Grasos
Farmacocinética
Roedores
Fatty Acids
Pharmacokinetics
Rodents
Fluoxetine
Omega-3
Efectos Antidepresivos
url https://www.sciencedirect.com/science/article/pii/S0022354915304020
http://hdl.handle.net/20.500.12123/2985
https://doi.org/10.1002/jps.24123
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