Abstract |
Drugs used to treat cancer have neurotoxic effects that often produce memory loss and related cognitive deficits. In a test of the hypothesis that chemotherapy-induced cognitive impairment is related to a loss of inhibitory control, rats injected with a combination of methotrexate+5-fluouracil or equal volumes of saline, were administered a retroactive interference task in which memory for a learned discrimination problem was tested under conditions of high- and low-interference. The drugs had no effect on original learning or on re-learning the discrimination response when there was little interference, but the chemotherapy group was severely impaired in the hippocampus-sensitive, high-interference memory test. The impaired performance correlated significantly with reduced neurogenesis in the hippocampus. The failure to suppress interfering influences is consistent with a breakdown in pattern separation, a process that distinguishes and separates overlapping neural representations of experiences that have a high degree of similarity.
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Authors | Gordon Winocur, J Martin Wojtowicz, Ian F Tannock |
Journal | Behavioural brain research
(Behav Brain Res)
Vol. 281
Pg. 239-44
(Mar 15 2015)
ISSN: 1872-7549 [Electronic] Netherlands |
PMID | 25529185
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier B.V. All rights reserved. |
Chemical References |
- Antimetabolites, Antineoplastic
- Antineoplastic Agents
- Fluorouracil
- Methotrexate
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Topics |
- Animals
- Antimetabolites, Antineoplastic
(adverse effects)
- Antineoplastic Agents
(adverse effects)
- Discrimination Learning
(drug effects)
- Female
- Fluorouracil
(adverse effects)
- Hippocampus
(drug effects, pathology)
- Maze Learning
(drug effects)
- Memory
(drug effects)
- Memory Disorders
(chemically induced, psychology)
- Methotrexate
(adverse effects)
- Neurogenesis
(drug effects)
- Neuropsychological Tests
- Psychomotor Performance
(drug effects)
- Rats
- Rats, Long-Evans
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