Fluoxetine counteracts the cognitive and cellular effects of 5-Fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery
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 impairmen...
| Main Authors: | , , , |
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| Format: | Article |
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Public Library of Science
2012
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| Online Access: | https://eprints.nottingham.ac.uk/2430/ |
| _version_ | 1848790783629459456 |
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| author | Lyons, Laura ELBeltagy, Maha Bennett, Geoffrey Wigmore, Peter |
| author_facet | Lyons, Laura ELBeltagy, Maha Bennett, Geoffrey Wigmore, Peter |
| author_sort | Lyons, Laura |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T18:18:06Z |
| format | Article |
| id | nottingham-2430 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:18:06Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-24302020-05-04T16:32:11Z https://eprints.nottingham.ac.uk/2430/ Fluoxetine counteracts the cognitive and cellular effects of 5-Fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery Lyons, Laura ELBeltagy, Maha Bennett, Geoffrey Wigmore, Peter 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. Public Library of Science 2012-01-17 Article PeerReviewed Lyons, Laura, ELBeltagy, Maha, Bennett, Geoffrey and Wigmore, Peter (2012) Fluoxetine counteracts the cognitive and cellular effects of 5-Fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery. PLoS ONE, 7 (1). e30010/1-e30010/8. ISSN 1932-6203 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030010 10.1371/journal.pone.0030010 10.1371/journal.pone.0030010 10.1371/journal.pone.0030010 |
| spellingShingle | Lyons, Laura ELBeltagy, Maha Bennett, Geoffrey Wigmore, Peter Fluoxetine counteracts the cognitive and cellular effects of 5-Fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery |
| title | Fluoxetine counteracts the cognitive and cellular effects of 5-Fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery |
| title_full | Fluoxetine counteracts the cognitive and cellular effects of 5-Fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery |
| title_fullStr | Fluoxetine counteracts the cognitive and cellular effects of 5-Fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery |
| title_full_unstemmed | Fluoxetine counteracts the cognitive and cellular effects of 5-Fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery |
| title_short | Fluoxetine counteracts the cognitive and cellular effects of 5-Fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery |
| title_sort | fluoxetine counteracts the cognitive and cellular effects of 5-fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery |
| url | https://eprints.nottingham.ac.uk/2430/ https://eprints.nottingham.ac.uk/2430/ https://eprints.nottingham.ac.uk/2430/ |