Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood

Abstract The objective of this study was to evaluate whether juvenile fluoxetine (FLX) exposure induces long-term changes in baseline responses to anxiety-inducing environments, and if so, whether its re-exposure in adulthood would ameliorate this anxiety-like phenotype. An additional goal was to as...

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Autores principales:	Francisco J. Flores-Ramirez, Anapaula Themann, Jorge A. Sierra-Fonseca, Israel Garcia-Carachure, Samuel A. Castillo, Minerva Rodriguez, Omar Lira, Joshua Preciado-Piña, Brandon L. Warren, Alfred J. Robison, Sergio D. Iñiguez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80c4ded134d041aa88cdd77b4d2e9863
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spelling	oai:doaj.org-article:80c4ded134d041aa88cdd77b4d2e98632021-12-02T18:15:25ZAdolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood10.1038/s41598-021-87378-62045-2322https://doaj.org/article/80c4ded134d041aa88cdd77b4d2e98632021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87378-6https://doaj.org/toc/2045-2322Abstract The objective of this study was to evaluate whether juvenile fluoxetine (FLX) exposure induces long-term changes in baseline responses to anxiety-inducing environments, and if so, whether its re-exposure in adulthood would ameliorate this anxiety-like phenotype. An additional goal was to assess the impact of adolescent FLX pretreatment, and its re-exposure in adulthood, on serotonin transporters (5-HTT) and brain-derived-neurotrophic-factor (BDNF)-related signaling markers (TrkB-ERK1/2-CREB-proBDNF-mBDNF) within the hippocampus and prefrontal cortex. To do this, female C57BL/6 mice were exposed to FLX in drinking water during postnatal-days (PD) 35–49. After a 21-day washout-period (PD70), mice were either euthanized (tissue collection) or evaluated on anxiety-related tests (open field, light/dark box, elevated plus-maze). Juvenile FLX history resulted in a persistent avoidance-like profile, along with decreases in BDNF-signaling markers, but not 5-HTTs or TrkB receptors, within both brain regions. Interestingly, FLX re-exposure in adulthood reversed the enduring FLX-induced anxiety-related responses across all behavioral tasks, while restoring ERK2-CREB-proBDNF markers to control levels and increasing mBDNF within the prefrontal cortex, but not the hippocampus. Collectively, these results indicate that adolescent FLX history mediates neurobehavioral adaptations that endure into adulthood, which are indicative of a generalized anxiety-like phenotype, and that this persistent effect is ameliorated by later-life FLX re-exposure, in a prefrontal cortex-specific manner.Francisco J. Flores-RamirezAnapaula ThemannJorge A. Sierra-FonsecaIsrael Garcia-CarachureSamuel A. CastilloMinerva RodriguezOmar LiraJoshua Preciado-PiñaBrandon L. WarrenAlfred J. RobisonSergio D. IñiguezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francisco J. Flores-Ramirez Anapaula Themann Jorge A. Sierra-Fonseca Israel Garcia-Carachure Samuel A. Castillo Minerva Rodriguez Omar Lira Joshua Preciado-Piña Brandon L. Warren Alfred J. Robison Sergio D. Iñiguez Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood
description	Abstract The objective of this study was to evaluate whether juvenile fluoxetine (FLX) exposure induces long-term changes in baseline responses to anxiety-inducing environments, and if so, whether its re-exposure in adulthood would ameliorate this anxiety-like phenotype. An additional goal was to assess the impact of adolescent FLX pretreatment, and its re-exposure in adulthood, on serotonin transporters (5-HTT) and brain-derived-neurotrophic-factor (BDNF)-related signaling markers (TrkB-ERK1/2-CREB-proBDNF-mBDNF) within the hippocampus and prefrontal cortex. To do this, female C57BL/6 mice were exposed to FLX in drinking water during postnatal-days (PD) 35–49. After a 21-day washout-period (PD70), mice were either euthanized (tissue collection) or evaluated on anxiety-related tests (open field, light/dark box, elevated plus-maze). Juvenile FLX history resulted in a persistent avoidance-like profile, along with decreases in BDNF-signaling markers, but not 5-HTTs or TrkB receptors, within both brain regions. Interestingly, FLX re-exposure in adulthood reversed the enduring FLX-induced anxiety-related responses across all behavioral tasks, while restoring ERK2-CREB-proBDNF markers to control levels and increasing mBDNF within the prefrontal cortex, but not the hippocampus. Collectively, these results indicate that adolescent FLX history mediates neurobehavioral adaptations that endure into adulthood, which are indicative of a generalized anxiety-like phenotype, and that this persistent effect is ameliorated by later-life FLX re-exposure, in a prefrontal cortex-specific manner.
format	article
author	Francisco J. Flores-Ramirez Anapaula Themann Jorge A. Sierra-Fonseca Israel Garcia-Carachure Samuel A. Castillo Minerva Rodriguez Omar Lira Joshua Preciado-Piña Brandon L. Warren Alfred J. Robison Sergio D. Iñiguez
author_facet	Francisco J. Flores-Ramirez Anapaula Themann Jorge A. Sierra-Fonseca Israel Garcia-Carachure Samuel A. Castillo Minerva Rodriguez Omar Lira Joshua Preciado-Piña Brandon L. Warren Alfred J. Robison Sergio D. Iñiguez
author_sort	Francisco J. Flores-Ramirez
title	Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood
title_short	Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood
title_full	Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood
title_fullStr	Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood
title_full_unstemmed	Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood
title_sort	adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female c57bl/6 mice that is ameliorated by fluoxetine re-exposure in adulthood
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/80c4ded134d041aa88cdd77b4d2e9863
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Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood

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