Preserved learning and memory in mice following chemotherapy: 5-Fluorouracil and doxorubicin single agent treatment, doxorubicin–cyclophosphamide combination treatment

Clinical studies suggest that chemotherapy is associated with long-term cognitive impairment in some patients. A number of underlying mechanisms have been proposed, however, the etiology of chemotherapy-related cognitive dysfunction remains relatively unknown. As part of a multifaceted approach, animal models of chemotherapy induced cognitive impairment are being developed. Thus far, the majority of animal studies have utilized rats, however, mice may prove particularly beneficial in studying genetic risk factors for developing chemotherapy induced cognitive impairment. Thus, C57BL/6J mice were treated once a week for three weeks with saline, doxorubicin and cyclophosphamide (D&C), doxorubicin (Dox), or 5-fluorouracil (5-FU). Recent and remote contextual fear conditioning and novel object recognition (NOR) was assessed. Despite significant toxic effects as assessed by weight loss, the chemotherapy treated mice performed as well as control mice on all task. As are some humans, C57BL/6J mice may be resistant to at least some aspects of chemotherapy induced cognitive decline.

► Chemotherapy is associated with cognitive impairments in a subset of cancer survivors.
► The etiology of chemotherapy-related cognitive dysfunction remains relatively unknown.
► The development of animal models will facilitate the search for the underlying mechanisms.
► Mouse and rat models of chemotherapy associated cognitive impairments may differ.
► As are some humans, C57BL/6J mice may be resistant to at least some aspects of chemotherapy induced cognitive decline.