TY - JOUR
T1 - Single high dose treatment with methotrexate causes long-lasting cognitive dysfunction in laboratory rodents
AU - Fardell, Joanna E.
AU - Vardy, Janette
AU - Logge, Warren
AU - Johnston, Ian
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
KW - chemotherapy
KW - methotrexate
KW - cognitive impairment
KW - memory
KW - executive function
KW - rat
UR - http://www.scopus.com/inward/record.url?scp=77957773399&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/arc/DP0667314
U2 - 10.1016/j.pbb.2010.08.019
DO - 10.1016/j.pbb.2010.08.019
M3 - Article
C2 - 20828582
AN - SCOPUS:77957773399
SN - 0091-3057
VL - 97
SP - 333
EP - 339
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 2
ER -