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Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus

The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLU, Prozac®) is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of se...

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Autores principales: Berg, Cecilia, Backström, Tobias, Winberg, Svante, Lindberg, Richard, Brandt, Ingvar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557231/
https://www.ncbi.nlm.nih.gov/pubmed/23383055
http://dx.doi.org/10.1371/journal.pone.0055053
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author Berg, Cecilia
Backström, Tobias
Winberg, Svante
Lindberg, Richard
Brandt, Ingvar
author_facet Berg, Cecilia
Backström, Tobias
Winberg, Svante
Lindberg, Richard
Brandt, Ingvar
author_sort Berg, Cecilia
collection PubMed
description The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLU, Prozac®) is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured)) on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks) until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation) of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.
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spelling pubmed-35572312013-02-04 Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus Berg, Cecilia Backström, Tobias Winberg, Svante Lindberg, Richard Brandt, Ingvar PLoS One Research Article The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLU, Prozac®) is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured)) on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks) until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation) of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife. Public Library of Science 2013-01-28 /pmc/articles/PMC3557231/ /pubmed/23383055 http://dx.doi.org/10.1371/journal.pone.0055053 Text en © 2013 Berg et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Berg, Cecilia
Backström, Tobias
Winberg, Svante
Lindberg, Richard
Brandt, Ingvar
Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus
title Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus
title_full Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus
title_fullStr Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus
title_full_unstemmed Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus
title_short Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus
title_sort developmental exposure to fluoxetine modulates the serotonin system in hypothalamus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557231/
https://www.ncbi.nlm.nih.gov/pubmed/23383055
http://dx.doi.org/10.1371/journal.pone.0055053
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