Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus

The hippocampal dentate gyrus has been implicated in a neuronal basis of antidepressant action. We have recently shown a distinct form of neuronal plasticity induced by the serotonergic antidepressant fluoxetine, that is, a reversal of maturation of the dentate granule cells in adult mice. This “dem...

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Main Authors:	Kobayashi, Katsunori, Ikeda, Yumiko, Asada, Minoru, Inagaki, Hirofumi, Kawada, Tomoyuki, Suzuki, Hidenori
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651130/

id	pubmed-3651130
recordtype	oai_dc
spelling	pubmed-36511302013-05-14 Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus Kobayashi, Katsunori Ikeda, Yumiko Asada, Minoru Inagaki, Hirofumi Kawada, Tomoyuki Suzuki, Hidenori Research Article The hippocampal dentate gyrus has been implicated in a neuronal basis of antidepressant action. We have recently shown a distinct form of neuronal plasticity induced by the serotonergic antidepressant fluoxetine, that is, a reversal of maturation of the dentate granule cells in adult mice. This “dematuration” is induced in a large population of dentate neurons and maintained for at least one month after withdrawal of fluoxetine, suggesting long-lasting strong influence of dematuration on brain functioning. However, reliable induction of dematuration required doses of fluoxetine higher than suggested optimal doses for mice (10 to 18 mg/kg/day), which casts doubt on the clinical relevance of this effect. Since our previous studies were performed in naive mice, in the present study, we reexamined effects of fluoxetine using mice treated with chronic corticosterone that model neuroendocrine pathophysiology associated with depression. In corticosterone-treated mice, fluoxetine at 10 mg/kg/day downregulated expression of mature granule cell markers and attenuated strong frequency facilitation at the synapse formed by the granule cell axon mossy fiber, suggesting the induction of granule cell dematuration. In addition, fluoxetine caused marked enhancement of dopaminergic modulation at the mossy fiber synapse. In vehicle-treated mice, however, fluoxetine at this dose had no significant effects. The plasma level of fluoxetine was comparable to that in patients taking chronic fluoxetine, and corticosterone did not affect it. These results indicate that corticosterone facilitates fluoxetine-induced plastic changes in the dentate granule cells. Our finding may provide insight into neuronal mechanisms underlying enhanced responsiveness to antidepressant medication in certain pathological conditions. Public Library of Science 2013-05-10 /pmc/articles/PMC3651130/ /pubmed/23675498 http://dx.doi.org/10.1371/journal.pone.0063662 Text en © 2013 Kobayashi 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kobayashi, Katsunori Ikeda, Yumiko Asada, Minoru Inagaki, Hirofumi Kawada, Tomoyuki Suzuki, Hidenori
spellingShingle	Kobayashi, Katsunori Ikeda, Yumiko Asada, Minoru Inagaki, Hirofumi Kawada, Tomoyuki Suzuki, Hidenori Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus
author_facet	Kobayashi, Katsunori Ikeda, Yumiko Asada, Minoru Inagaki, Hirofumi Kawada, Tomoyuki Suzuki, Hidenori
author_sort	Kobayashi, Katsunori
title	Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus
title_short	Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus
title_full	Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus
title_fullStr	Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus
title_full_unstemmed	Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus
title_sort	corticosterone facilitates fluoxetine-induced neuronal plasticity in the hippocampus
description	The hippocampal dentate gyrus has been implicated in a neuronal basis of antidepressant action. We have recently shown a distinct form of neuronal plasticity induced by the serotonergic antidepressant fluoxetine, that is, a reversal of maturation of the dentate granule cells in adult mice. This “dematuration” is induced in a large population of dentate neurons and maintained for at least one month after withdrawal of fluoxetine, suggesting long-lasting strong influence of dematuration on brain functioning. However, reliable induction of dematuration required doses of fluoxetine higher than suggested optimal doses for mice (10 to 18 mg/kg/day), which casts doubt on the clinical relevance of this effect. Since our previous studies were performed in naive mice, in the present study, we reexamined effects of fluoxetine using mice treated with chronic corticosterone that model neuroendocrine pathophysiology associated with depression. In corticosterone-treated mice, fluoxetine at 10 mg/kg/day downregulated expression of mature granule cell markers and attenuated strong frequency facilitation at the synapse formed by the granule cell axon mossy fiber, suggesting the induction of granule cell dematuration. In addition, fluoxetine caused marked enhancement of dopaminergic modulation at the mossy fiber synapse. In vehicle-treated mice, however, fluoxetine at this dose had no significant effects. The plasma level of fluoxetine was comparable to that in patients taking chronic fluoxetine, and corticosterone did not affect it. These results indicate that corticosterone facilitates fluoxetine-induced plastic changes in the dentate granule cells. Our finding may provide insight into neuronal mechanisms underlying enhanced responsiveness to antidepressant medication in certain pathological conditions.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651130/
_version_	1611976988721938432

Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus

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