ArticlePloS one2012
Fluoxetine counteracts the cognitive and cellular effects of 5-fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 85 citations in OpenAlex.
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- Chemotherapy-Induced Brain Damage: Mechanisms and Insights from Rodent Models.Brain sciences · 2026Review
- Mechanistic insights and therapeutic interventions of mitochondrial quality control in chemotherapy-related cognitive impairment.Neoplasia (New York, N.Y.) · 2026Review
- Advances in neuroimaging in cancer-related cognitive impairment.Frontiers in human neuroscience · 2026Review
- Mechanisms and treatment of cancer therapy-induced peripheral and central neurotoxicity.Nature reviews. Cancer · 2025Review
- Microglia-Mediated Synaptic Dysfunction Contributes to Chemotherapy-Related Cognitive Impairment.Journal of neurochemistry · 2025Article
- Coenzyme Q10 ameliorates chemotherapy-induced cognitive impairment in mice: a preclinical study.Molecular biology reports · 2024Article
- In-vitro and in-vivo studies of two-drug cocktail therapy targeting chemobrain via the Nrf2/NF-κB signaling pathway.Journal of molecular histology · 2024Article
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- Cancer related cognitive impairment: a downside of cancer treatment.Frontiers in oncology · 2024Review
- [Immunological mechanisms of cognitive dysfunction under systemic therapy in metastatic melanoma].Dermatologie (Heidelberg, Germany) · 2022Review
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- Cognitive adverse effects of chemotherapy and immunotherapy: are interventions within reach?Nature reviews. Neurology · 2022Review
- Effects of Endocrine Therapy on Cognitive Function in Patients with Breast Cancer: A Comprehensive Review.Cancers · 2022Review
- Melatonin Attenuates Methotrexate-Induced Reduction of Antioxidant Activity Related to Decreases of Neurogenesis in Adult Rat Hippocampus and Prefrontal Cortex.Oxidative medicine and cellular longevity · 2022Article
- Structural and functional brain alterations associated with cancer-associated cognitive decline in gastric cancer patients: A preliminary longitudinal neuroimaging study.Brain and behavior · 2022Article
- Four decades of chemotherapy-induced cognitive dysfunction: comprehensive review of clinical, animal and in vitro studies, and insights of key initiating events.Archives of toxicology · 2022Review
- A narrative review of genetic factors affecting fluoropyrimidine toxicity.Precision cancer medicine · 2021Article
- Chemotherapy-Induced Cognitive Impairment and Hippocampal Neurogenesis: A Review of Physiological Mechanisms and Interventions.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
5-Fluorouracil (5-FU) is a cytostatic drug associated with chemotherapy-induced cognitive impairments that many cancer patients experience after treatment. Previous work in rodents has shown that 5-FU reduces hippocampal cell proliferation, a possible mechanism for the observed cognitive impairment, and that both effects can be reversed by co-administration of the antidepressant, fluoxetine. In the present study we investigate the optimum time for administration of fluoxetine to reverse or prevent the cognitive and cellular effects of 5-FU. Male Lister-hooded rats received 5 injections of 5-FU (25 mg/kg, i.p.) over 2 weeks. Some rats were co-administered with fluoxetine (10 mg/kg/day, in drinking water) for 3 weeks before and during (preventative) or after (recovery) 5-FU treatment or both time periods (throughout). Spatial memory was tested using the novel location recognition (NLR) test and proliferation and survival of hippocampal cells was quantified using immunohistochemistry. 5-FU-treated rats showed cognitive impairment in the NLR task and a reduction in cell proliferation and survival in the subgranular zone of the dentate gyrus, compared to saline treated controls. These impairments were still seen for rats administered fluoxetine after 5-FU treatment, but were not present when fluoxetine was administered both before and during 5-FU treatment. The results demonstrate that fluoxetine is able to prevent but not reverse the cognitive and cellular effects of 5-FU. This provides information on the mechanism by which fluoxetine acts to protect against 5-FU and indicates when it would be beneficial to administer the antidepressant to cancer patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.