, Volume 232, Issue 1, pp 17–37 | Cite as

Cognitive impact of cytotoxic agents in mice

  • R. Seigers
  • M. Loos
  • O. Van Tellingen
  • W. Boogerd
  • A. B. Smit
  • S. B. SchagenEmail author
Original Investigation


Rationale and objectives

Adjuvant chemotherapy is associated with changes in cognition in a subgroup of cancer patients. Chemotherapy is generally given as a combination of cytotoxic agents, which makes it hard to define the agent responsible for these observed changes. Literature on animal experiments has been difficult to interpret due to variance in experimental setup.


We examined the effects of cytotoxic agents administered separately on various cognitive measures in a standardized animal model. Male C57Bl/6 mice received cyclophosphamide, docetaxel, doxorubicin, 5-fluorouracil, methotrexate, or topotecan. These agents represent different compound classes based on their working mechanism and are frequently prescribed in the clinic. A control group received saline. Behavioral testing started 2 or 15 weeks after treatment and included testing general measures of behavior and cognitive task performance: spontaneous behavior in an automated home cage, open field, novel location recognition (NLR), novel object recognition (NOR), Barnes maze, contextual fear conditioning, and a simple choice reaction time task (SCRTT).


Cyclophosphamide, docetaxel, and doxorubicin administration affected spontaneous activity in the automated home cage. All cytotoxic agents affected memory (NLR and/or NOR). Spatial memory measured in the Barnes maze was affected after administration with doxorubicin, 5-fluorouracil, and topotecan. Decreased inhibition in the SCRTT was observed after treatment with cyclophosphamide, docetaxel, and topotecan.


Our data show that, in mice, a single treatment with a cytotoxic agent causes cognitive impairment. Not all cytotoxic agents affected the same cognitive domains, which might be explained by differences in working mechanisms of the various agents.


Mice Chemotherapy Cytotoxic agent Behavior Cognition 



The authors declare that the experiments performed in this manuscript are in compliance with the current laws of The Netherlands.


This research was funded by the Dutch Cancer Society, grant number NKI 2010-4829.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • R. Seigers
    • 1
  • M. Loos
    • 2
  • O. Van Tellingen
    • 3
  • W. Boogerd
    • 4
  • A. B. Smit
    • 5
  • S. B. Schagen
    • 1
    Email author
  1. 1.Department of Psychosocial Research and EpidemiologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Sylics (Synaptologics BV)AmsterdamThe Netherlands
  3. 3.Division of Molecular BiologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  4. 4.Department of Neuro-OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  5. 5.Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus AmsterdamVU UniversityAmsterdamThe Netherlands

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