Cognitive impairments caused by oxaliplatin and 5-fluorouracil chemotherapy are ameliorated by physical activity

Joanna E. Fardell, Janette Vardy, Jeanette D. Shah, Ian N. Johnston

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)

Abstract

Rationale: Studies in women with breast cancer, and in animal models, have demonstrated that chemotherapy can have a negative impact on cognitive function. Which chemotherapy agents cause problems with cognition and the aetiology of the impairment is unknown. Furthermore, there is no proven treatment. Objectives: This study aimed to evaluate the effects of 5-fluorouracil (5FU) and oxaliplatin (OX) chemotherapy agents commonly used to treat colorectal cancer on cognition in laboratory rodents. Furthermore, we assessed physical activity as a potential remedy for the observed chemotherapy-induced cognitive deficits. Results: In rodents, treatment with 5FU and OX alone impairs memory as measured by novel object recognition. But combined treatment appears to have greater detrimental effects on hippocampal-dependent tasks, contextual fear recall and spatial reference memory (water maze), yet had no effect on cued fear recall, a non-hippocampal task. These impairments were prevented by 4 weeks of wheel running overnight after 5FU/OX treatment. We found a significant interaction between chemotherapy and exercise: rats receiving both 5FU/OX and exercise had improved cognition relative to non-exercising 5FU/OX rats on novel object recognition and spatial reference memory. Conclusions: The combination 5FU/OX had a significant impact on cognition. However, rats treated with 5FU/OX that exercised post chemotherapy had improved cognition relative to non-exercising rats. This suggests that physical activity may prove useful in ameliorating the cognitive impairments induced by 5FU/OX.
Original languageEnglish
Pages (from-to)183-193
Number of pages11
JournalPsychopharmacology
Volume220
Issue number1
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • chemotherapy
  • cognition
  • oxaliplatin
  • 5-fluorouracil
  • exercise

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