Cited by 56Treatment of Major DepressionNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

Fluoxetine administration modulates the cytoskeletal microtubular system in the rat hippocampus

Bianchi, Massimiliano, Shah, Ajit J., Fone, Kevin C.F., Atkins, Alan R., Dawson, Lee A., Heidbreder, Christian A., Hows, Mark E., Hagan, Jim J. +1 more·2009·Synapse

Abstract

A number of studies suggest that stressful conditions can induce structural alterations in the hippocampus and that antidepressant drugs may prevent such deficits. In particular, the selective serotonin reuptake inhibitor (SSRI) fluoxetine was more effective in modulating different neuronal plasticity phenomena and related molecules in rat hippocampus. Cytoskeletal microtubule dynamics are fundamental to dendrites and axons remodeling, leading to the hypothesis that fluoxetine may affect the microtubular system. However, despite reports of stress-induced alterations in microtubule dynamics by different stressors, only few studies investigated the in vivo effects of antidepressants on microtubules in specific rat brain regions. The present study investigated the dose-related (1, 5, or 10 mg/kg i.p.) effects of acute and chronic (21 days) treatments with fluoxetine on the ratio of hippocampal alpha-tubulin isoforms which is thought to reflect microtubule dynamics. Western Blot analysis was used to quantify alpha-tubulin isoforms, high-performance liquid chromatography and fluorescence detection was used to measure ex vivo monoamine metabolism. The results showed that acute fluoxetine increased the stable forms acetylated and detyrosinated alpha-tubulin. Conversely, chronic fluoxetine decreased acetylated alpha-tubulin, indicative of increased microtubule dynamics. The neuron-specific Delta2-Tubulin was increased by chronic fluoxetine indicating neuronal involvement in the observed cytoskeletal changes. Although acute and chronic fluoxetine similarly altered serotonin metabolism by inhibition of serotonin reuptake, this showed no apparent correlation to the cytoskeletal perturbations. Our findings demonstrate that fluoxetine administration modulates microtubule dynamics in rat hippocampus. The cytoskeletal effect exerted by fluoxetine may eventually culminate in promoting events of structural neuronal remodeling.

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Crossref · 10.1002/syn.20614

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  • Fluoxitene (Prozac) acts through microtubules.

    “Fluoxitene (Prozac) acts through microtubules [167]”

    From Consciousness in the universe (2014) · cites this paper as [167]

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Authors
Bianchi, M., Shah, A. J., Fone, K. C. F., Atkins, A. R., Dawson, L. A., Heidbreder, C. A., Hows, M. E., Hagan, J. J., & Marsden, C. A.
Affiliations
  • University of Nottingham (GB)
  • GlaxoSmithKline (United Kingdom) (GB)
  • GlaxoSmithKline (Italy) (IT)
Corresponding author
Bianchi, Massimiliano
Venue
Synapse
Publisher
Wiley
Published
2009-01-12
Volume
63
Issue
4
Pages
359-364
ISSN
  • 0887-4476 (ISSN-L)
  • 1098-2396
OpenAlex
W2008458074
Cited by
56
References
27
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 2 · 2013: 3 · 2012: 5
FWCI
3.83
Type
journal article
Language
en
Open access
closed
Locations
  • Synapse (publishedVersion)
  • PubMed (publishedVersion)
  • Middlesex University Research Repository (Middlesex University Of London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
fluoxetine, microtubule dynamics, hippocampus, acetylated alpha-tubulin, selective serotonin reuptake inhibitors, antidepressant effects, serotonin metabolism, neuroplasticity
MeSH terms
Animals, Cytoskeleton, Dose-Response Relationship, Drug, Fluoxetine, Hippocampus, Male, Microtubules, Time Factors, Selective Serotonin Reuptake Inhibitors, Rats

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