Single high dose treatment with methotrexate causes long-lasting cognitive dysfunction in laboratory rodents

Joanna E. Fardell*, Janette Vardy, Warren Logge, Ian Johnston

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Clinical studies have suggested that cognitive impairment due to chemotherapy persists long after treatment cessation. While animal studies have similarly found impairments in cognition due to chemotherapy, these studies are limited as they only assess the acute or extremely short-term effects of chemotherapy on cognition (e.g. within 1. month of treatment). Male hooded Wistar rats (N = 22) received either a high dose of methotrexate (MTX: 250. mg/kg i.p.) or physiological saline. Cognitive performance was evaluated acutely at 2. weeks, and up to 8. months post injection using the Morris water maze, Novel object recognition task, and an instrumental go/no-go task to assess discrimination learning. MTX-treated rats displayed impaired novel object recognition compared to controls at 11, 95, and 255. days after treatment. MTX rats were able to learn the hidden spatial location of a platform 22. days after treatment. When tested again after a 95-day retention interval, MTX rats showed impaired spatial memory compared to controls, but were subsequently able to re-learn the task. Finally, MTX-treated rats showed considerable difficulty learning to inhibit their behaviour in an instrumental discrimination task. These results show that chemotherapy produces persistent but subtle cognitive deficits in laboratory rodents that vary with time post treatment.

Original languageEnglish
Pages (from-to)333-339
Number of pages7
JournalPharmacology Biochemistry and Behavior
Issue number2
Publication statusPublished - Dec 2010
Externally publishedYes


  • chemotherapy
  • methotrexate
  • cognitive impairment
  • memory
  • executive function
  • rat


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