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Molecular Brain

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Open Access 01-12-2011 | Research

Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine

Authors: Katsunori Kobayashi, Yumiko Ikeda, Hidenori Suzuki

Published in: Molecular Brain | Issue 1/2011

Abstract

Background

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat mood and anxiety disorders. However, neuronal bases for both beneficial and adverse effects of SSRIs remain poorly understood. We have recently shown that the SSRI fluoxetine can reverse the state of maturation of hippocampal granule cells in adult mice. The granule cell "dematuration" is induced in a large population of granule cells, and greatly changes functional and physiological properties of these cells. Here we show that this unique form of neuronal plasticity is correlated with a distinct change in behavior of mice.

Results

We chronically treated adult male mice with fluoxetine, and examined its effect on several forms of behavior of mice. During fluoxetine treatments, mice showed a marked increase in day-to-day fluctuations of home cage activity levels that was characterized by occasional switching between hypoactivity and hyperactivity within a few days. This destabilized cage activity was accompanied by increased anxiety-related behaviors and could be observed up to 4 weeks after withdrawal from fluoxetine. As reported previously, the granule cell dematuration by fluoxetine includes a reduction of synaptic facilitation at the granule cell output, mossy fiber, synapse to the juvenile level. Mossy fiber synaptic facilitation examined electrophysiologically in acute hippocampal slices also remained suppressed after fluoxetine withdrawal and significantly correlated with the fluctuation of cage activity levels in individual mice. Furthermore, in mice lacking the 5-HT₄ receptor, in which the granule cell dematuration has been shown to be attenuated, fluoxetine had no significant effect on the fluctuation of cage activity levels.

Conclusions

Our results demonstrate that the SSRI fluoxetine can induce marked day-to-day changes in activity levels of mice in the familiar environment, and that the dematuration of the hippocampal granule cells is closely associated with the expression of this destabilized behavior. Based on these results, we propose that the granule cell dematuration can be a potential cellular basis underlying switching-like changes in the behavioral state associated with SSRI treatments.

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Title: Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine
Authors: Katsunori Kobayashi
Yumiko Ikeda
Hidenori Suzuki
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Molecular Brain / Issue 1/2011
Electronic ISSN: 1756-6606
DOI: https://doi.org/10.1186/1756-6606-4-12

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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