ArticleMolecular brain2011
Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine.
Article in Molecular brain, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 42 citations in OpenAlex.
- Hyper-maturity and accelerated aging in the hippocampus of mouse models of neuropsychiatric disorders with anxiety-like behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The potential role of Saiko-ka-ryukotsu-borei-to in mitigating the severity of anxiety induced by social defeat stress in mice.PCN reports : psychiatry and clinical neurosciences · 2025Article
- Role of desmoplakin in supporting neuronal activity, neurogenic processes, and emotional-related behaviors in the dentate gyrus.Frontiers in neuroscience · 2024Article
- Noradrenaline activation of hippocampal dopamine DProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Serotonin receptor 4 in the hippocampus modulates mood and anxiety.Molecular psychiatry · 2021Article
- Rewiring of the Serotonin System in Major Depression.Frontiers in psychiatry · 2021Review
- Predominant Role of Serotonin at the Hippocampal Mossy Fiber Synapse with Redundant Monoaminergic Modulation.iScience · 2020Article
- Transcriptomic evidence for immaturity induced by antidepressant fluoxetine in the hippocampus and prefrontal cortex.Neuropsychopharmacology reports · 2019Article
- iPlasticity: Induced juvenile-like plasticity in the adult brain as a mechanism of antidepressants.Psychiatry and clinical neurosciences · 2018Review
- Prodepressant- and anxiogenic-like effects of serotonin-selective, but not noradrenaline-selective, antidepressant agents in mice lacking α2-containing GABABehavioural brain research · 2017Article
- Activity modifies adult brain maturity.Oncotarget · 2017Article
- Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment.Molecular brain · 2017Article
- The Effect of Serotonin-Targeting Antidepressants on Neurogenesis and Neuronal Maturation of the Hippocampus Mediated via 5-HT1A and 5-HT4 Receptors.Frontiers in cellular neuroscience · 2017Review
- 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response.Nature neuroscience · 2015Article
- Mechanisms underlying the neuroprotective effect of brain reserve against late life depression.Journal of neural transmission (Vienna, Austria : 1996) · 2015Review
- Role of the 5-HT4 receptor in chronic fluoxetine treatment-induced neurogenic activity and granule cell dematuration in the dentate gyrus.Molecular brain · 2015Article
- Chronic fluoxetine treatment reduces parvalbumin expression and perineuronal nets in gamma-aminobutyric acidergic interneurons of the frontal cortex in adult mice.Molecular brain · 2013Article
- Synaptosomal-associated protein 25 mutation induces immaturity of the dentate granule cells of adult mice.Molecular brain · 2013Article
- Immature dentate gyrus: an endophenotype of neuropsychiatric disorders.Neural plasticity · 2013Review
- Corticosterone facilitates fluoxetine-induced neuronal plasticity in the hippocampus.PloS one · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSelective 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.
resultsWe 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.
conclusionsOur 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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