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Cited by 96Neurogenesis and neuroplasticity mechanismsTreatment of Major DepressionNeuroscience and Neuropharmacology Research

Comparison of neurogenic effects of fluoxetine, duloxetine and running in mice

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Marlatt, Michael W., Lucassen, Paul J., van Praag, Henriette·2010·Brain Research
DOI 10.1016/j.brainres.2010.03.086PMC PMC2884062
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Abstract

Hippocampal neurogenesis can be regulated by extrinsic factors, such as exercise and antidepressants. While there is evidence that the selective serotonin reuptake inhibitor (SSRI) fluoxetine enhances neurogenesis, the new dual serotonergic-noradrenergic reuptake inhibitor (SNRI) duloxetine has not been evaluated in this context. In addition, it is unclear whether effects of antidepressants and running on cell genesis and behavior are of similar magnitude in mice. Here, we assessed neurogenesis and open-field behavior in 2-month-old female C57Bl/6 mice after 28days of treatment with either fluoxetine (18mg/kg), duloxetine (2, 6 or 18mg/kg) or exercise. New cell survival, as measured by 5-bromo-2'-deoxyuridine (BrdU)-labeled cells, was enhanced by 200% in the running group only. Both running and fluoxetine, but not duloxetine, increased the percentage of new cells that became neurons. In the open-field test, animals treated with either drug spent less time in the center than controls and runners. In addition, fluoxetine treatment resulted in reduced locomotor activity. Together, these data show that the neurogenic response to exercise is much stronger than to antidepressants and imply a low likelihood that anxiolytic effects of these drugs are mediated by adult neurogenesis in C57Bl/6 mice.

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  • Fluoxetine may be more effective on symptoms related to anxiety/depression rather than to memory, at least in tests on mice, such as the open field test, where running is inactive.

    “In this respect, fluoxetine may be more effective on symptoms related to anxiety/depression rather than to memory, at least in tests on mice, such as defined by the open field test, which measures anxiety and where running is inactive (Marlatt et al., 2010).”

    From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Marlatt et al., 2010

    The Results (§2.1 Behavior; page unavailable) explicitly conclude that fluoxetine had no anxiolytic effect in the open-field test in female C57Bl/6 mice, contrary to the claimed advantage for anxiety-related symptoms. The Discussion (§3; page unavailable) supports only the narrower point that runners did not differ from controls in open-field behavior. The study does not report a memory comparison. (LLM, conf=0.88)

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  • Neurogenic effects of SSRIs vary between substances.

    “Neurogenic effects of SSRIs vary between substances (Marlatt et al., 2010), the SERT and BDNF play a crucial role (Benninghoff et al., 2012;Homberg et al., 2014;Sairanen et al., 2005) and 5-HT 1A and 5-HT 4 receptors might mediate consecutive changes in gene expression (see Table 1; Gaspar et al., 2003;Lesch, 2001).”

    From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Marlatt et al., 2010

    The Discussion reports different neurogenic effects for fluoxetine and duloxetine, and says antidepressant effects vary with pharmacology. But fluoxetine is an SSRI and duloxetine is an SNRI; the paper does not establish variation between different SSRIs. Page numbers were not available in our copy. (LLM, conf=0.88)

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  • In animals, AE was significantly more potent at increasing the survival of adult-born granule cells than SSRIs like fluoxetine and duloxetine.

    “Additionally, in animals, AE was significantly more potent at increasing the survival of adult-born granule cells in comparison to SSRIs like fluoxetine and duloxetine (Marlatt et al., 2010).”

    From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Marlatt et al., 2010

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Authors
Marlatt, M. W., Lucassen, P. J., & van Praag, H.
Affiliations
  • National Institute on Aging (US)
  • University of Amsterdam (NL)
ORCID
Lucassen, Paul J.
Venue
Brain Research
Publisher
Elsevier BV
Published
2010-06
Volume
1341
Pages
93-99
ISSN
0006-8993 (ISSN-L)
DOI
10.1016/j.brainres.2010.03.086
PMC
PMC2884062
OpenAlex
W2058868956
Cited by
96
References
58
Citations by year
2025: 1 · 2024: 3 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 11 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 11 · 2012: 15
FWCI
3.84
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
  • UvA-DARE (University of Amsterdam) (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • European Commission
  • Internationale Stichting Alzheimer Onderzoek
  • National Institutes of Health
  • National Institute on Aging (ZIAAG000328)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
hippocampal neurogenesis, adult neurogenesis, fluoxetine, duloxetine, physical activity, running, selective serotonin reuptake inhibitors, antidepressants, BrdU labeling, open field behavior, locomotor activity, anxiolytic effects, C57BL/6 mice
MeSH terms
Duloxetine Hydrochloride, Animals, Behavior, Animal, Cell Survival, Female, Fluoxetine, Hippocampus, Mice, Inbred C57BL, Motor Activity, Neuronal Plasticity, Neurons, Physical Conditioning, Animal, Thiophenes, Selective Serotonin Reuptake Inhibitors, Cell Proliferation, Mice, Neurogenesis

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