Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or m...

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Main Authors: Jodi L. Pawluski, Eva van Donkelaar, Zipporah Abrams, Virginie Houbart, Marianne Fillet, Harry W. M. Steinbusch, Thierry D. Charlier
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2014/123026
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author Jodi L. Pawluski
Eva van Donkelaar
Zipporah Abrams
Virginie Houbart
Marianne Fillet
Harry W. M. Steinbusch
Thierry D. Charlier
author_facet Jodi L. Pawluski
Eva van Donkelaar
Zipporah Abrams
Virginie Houbart
Marianne Fillet
Harry W. M. Steinbusch
Thierry D. Charlier
author_sort Jodi L. Pawluski
collection DOAJ
description Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat.
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spelling doaj-art-13c217d001544a9e890ba5df1e552d742025-02-03T05:47:48ZengWileyNeural Plasticity2090-59041687-54432014-01-01201410.1155/2014/123026123026Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female RatsJodi L. Pawluski0Eva van Donkelaar1Zipporah Abrams2Virginie Houbart3Marianne Fillet4Harry W. M. Steinbusch5Thierry D. Charlier6GIGA-Neurosciences, University of Liège, 1 Avenue de l’Hôpital, Bâtiment B36, 4000 Liège, BelgiumSchool for Mental Health and Neuroscience, Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, The NetherlandsDepartment of Biological Sciences, Irvine Hall, Ohio University, Athens, OH 45701, USALaboratory of Analytical Pharmaceutical Chemistry, Department of Pharmacy, CIRM, University of Liège, 1 Avenue de l’Hôpital, Bâtiment B36, 4000 Liège, BelgiumLaboratory of Analytical Pharmaceutical Chemistry, Department of Pharmacy, CIRM, University of Liège, 1 Avenue de l’Hôpital, Bâtiment B36, 4000 Liège, BelgiumSchool for Mental Health and Neuroscience, Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, The NetherlandsGIGA-Neurosciences, University of Liège, 1 Avenue de l’Hôpital, Bâtiment B36, 4000 Liège, BelgiumSelective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat.http://dx.doi.org/10.1155/2014/123026
spellingShingle Jodi L. Pawluski
Eva van Donkelaar
Zipporah Abrams
Virginie Houbart
Marianne Fillet
Harry W. M. Steinbusch
Thierry D. Charlier
Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats
Neural Plasticity
title Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats
title_full Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats
title_fullStr Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats
title_full_unstemmed Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats
title_short Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats
title_sort fluoxetine dose and administration method differentially affect hippocampal plasticity in adult female rats
url http://dx.doi.org/10.1155/2014/123026
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