title: Memory loss in chemotherapy-treated rats is exacerbated in high-interference conditions and related to suppression of hippocampal neurogenesis.
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.
authors.affiliation: Rotman Research Institute, Baycrest Centre, 3560 Bathurst Street, Toronto, ON M6A 2E1, Canada; Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, M5T1X8, Canada; Department of Psychology, Trent University, 1600 West Bank Dr, Peterborough, ON K9J 7B8, Canada. Electronic address: gwinocur@research.baycrest.org.
authors.forename: Gordon
authors.initials: G
authors.lastname: Winocur
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON M5S 1E8, Canada.
authors.forename: J Martin
authors.initials: JM
authors.lastname: Wojtowicz
authors.affiliation: Department of Medical Oncology, University of Toronto, Princess Margaret Hospital, 610 University Ave, Toronto, ON M5G 2M9, Canada; Department of Medical Biophysics, University of Toronto, Princess Margaret Hospital, 610 University Ave, Toronto, ON M5G 2M9, Canada.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004193:Discrimination Learning / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology; D008727:Methotrexate / Q000009:adverse effects; D055495:Neurogenesis / Q000187:drug effects*; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005472:Fluorouracil; D008727:Methotrexate
keywords: Chemotherapy; Interference; Memory loss; Neurogenesis