Chronic treatment with fluoxetine up-regulates cellular BDNF mRNA expression in rat dopaminergic regions
Open accessAbstract
During the last few years several studies have highlighted the possibility that major depression can be characterized by a general reduction in brain plasticity and an increased vulnerability under challenging situations. Such dysfunction may be the consequence of reduced expression and function of proteins important for neuroplasticity such as brain-derived neurotrophic factor (BDNF). On this basis, by using a sensitive non-radioactive in-situ hybridization, we evaluated the effects of a chronic treatment with fluoxetine on BDNF expression within rat dopaminergic regions. In fact, besides the well-established role of the hippocampus, increasing evidence indicates that other brain regions may be involved in the pathophysiology of depression and consequently be relevant for the therapeutic action of antidepressant drugs. Our results indicate that 3 wk of fluoxetine administration up-regulates BDNF mRNA levels selectively within structures belonging to the meso-cortico-limbic pathway. The expression of the neurotrophin is significantly increased in the ventral tegmental area, prefrontal cortex, and shell region of the nucleus accumbens, whereas no changes were detected in the substantia nigra and striatum. Moreover, in agreement with previous studies, fluoxetine increased BDNF mRNA levels in the hippocampus, an effect that was limited to the cell bodies without any change in its dendritic targeting. These data show that chronic treatment with fluoxetine increases BDNF gene expression not only in limbic areas but also in dopaminergic regions, suggesting that such an effect may contribute to improve the function of the dopaminergic system in depressed subjects.
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Fluoxetine induces the expression of BDNF in dentate gyrus cells, where it exerts a marked influence on their maturation.
“This pro-differentiation effect is also in line with the finding that fluoxetine induces the expression of BDNF in dentate gyrus cells, where it exerts a marked influence on their maturation (Molteni et al., 2006;Waterhouse et al., 2012).”
From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Molteni et al., 2006
The Results report that chronic fluoxetine increased BDNF mRNA in rat dentate gyrus granule-cell bodies by 15%. The paper does not establish that BDNF exerts a marked influence on those cells’ maturation; its Introduction discusses maturation of midbrain dopaminergic neurons instead. The measured increase was in mRNA, not BDNF protein. (LLM, conf=0.88)
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- Authors
- Molteni, R., Calabrese, F., Bedogni, F., Tongiorgi, E., Fumagalli, F., Racagni, G., & Andrea Riva, M.
- Affiliations
- University of Milan (IT)
- Centro San Giovanni di Dio Fatebenefratelli (IT)
- University of Trieste (IT)
- ORCID
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-07-22
- Volume
- 9
- Issue
- 03
- Pages
- 307
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2150640010
- Semantic Scholar
- d7ad09cc1a99d466f6bd0bc6306535905dae0530
- Cited by
- 132
- References
- 55
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 3 · 2022: 10 · 2021: 4 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 11 · 2016: 4 · 2015: 4 · 2014: 10 · 2013: 6 · 2012: 9
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- fluoxetine, brain-derived neurotrophic factor, BDNF mRNA expression, major depressive disorder, antidepressant mechanism, ventral tegmental area, prefrontal cortex, nucleus accumbens shell, hippocampus, neuroplasticity, substantia nigra, striatum
- MeSH terms
- Animals, Brain, Cytoplasm, Dopamine, Fluoxetine, Gene Expression Regulation, Male, RNA, Messenger, Up-Regulation, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Rats
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