title: Donepezil reduces cognitive impairment associated with anti-cancer drugs in a mouse model.
abstract: Adjuvant cancer chemotherapy often causes cognitive impairment that can be long-lasting and adversely affect quality of life. The present study sought to determine if the cognitive enhancing drug, donepezil, can reduce cognitive impairment induced by a combination of methotrexate +5-fluorouracil, two drugs commonly used in cancer chemotherapy. Four groups of mice: (1) chemotherapy-only; (2) chemotherapy+donepezil; (3) saline-only; (4) saline+donepezil, were administered the following learning and memory tests: (1) standard spatial memory (SM); (2) non-spatial cued memory (CM); (3) non-matching-to-sample (NMTS) rule-learning; (4) delayed-NMTS (DNMTS). The chemotherapy-only group was impaired on the SM, NMTS, and DNMTS tasks. Chemotherapy-induced cognitive deficits were significantly reduced in the chemotherapy+donepezil group whose performance on some measures was very similar to that of the saline-only group. There was no evidence that donepezil improved the performance of saline-treated mice. The results confirm the adverse effects of chemotherapy on cognitive function and demonstrate that they can be ameliorated by donepezil, which is widely used to treat cognitive impairment in other clinical populations (e.g., Alzheimer's disease).
authors.affiliation: Rotman Research Institute, Baycrest Centre, 3560 Bathurst Street, Toronto, ON M6A 2E1, Canada. gwinocur@rotman-baycrest.on.ca
authors.forename: Gordon
authors.initials: G
authors.lastname: Winocur
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Binns
authors.forename: Ian
authors.initials: I
authors.lastname: Tannock
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D003463:Cues; D004195:Disease Models, Animal; D000077265:Donepezil; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D007189:Indans / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008727:Methotrexate / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D013028:Space Perception / Q000187:drug effects; D013997:Time Factors
chemical_list: D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil; D005472:Fluorouracil; D008727:Methotrexate