期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 107, 期 -, 页码 296-304出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2022.10.018
关键词
Cancer; Chemoradiation; Survivorship; Fatigue; Associative learning; Conditioned responses
A study was conducted using a murine model of cancer survivorship to investigate the role of associative learning in the persistence of fatigue. The results showed that re-exposure to a treatment-related olfactory cue could acutely reinstate fatigue. This is the first demonstration that associative processes can modulate the persistence of cancer-related fatigue-like behavior.
Persistent fatigue is a debilitating side effect that impacts a significant proportion of cancer survivors for which there is not yet an FDA-approved treatment. While certainly a multi-factorial problem, persistent fatigue could be due, in part, to associations learned during treatment. Therefore, we sought to investigate the role of associative learning in the persistence of fatigue using a preclinical model of cancer survivorship. For this purpose, we used a murine model of human papilloma virus-related head and neck cancer paired with a curative regimen of cisplatin-based chemoradiation in male C57BL/6J mice. Fatigue-like behavior was assessed by measuring vari-ations in voluntary wheel running using a longitudinal design. Treatment robustly decreased voluntary wheel running, and this effect persisted for more than a month posttreatment. However, when wheels were removed during treatment, to minimize treatment-related fatigue, mice showed a more rapid return to baseline running levels. We confirmed that the delayed recovery observed in mice with continual wheel access was not due to increased treatment-related toxicity, in fact running attenuated cisplatin-induced kidney toxicity. Finally, we demonstrated that re-exposure to a treatment-related olfactory cue acutely re-instated fatigue. These data pro-vide the first demonstration that associative processes can modulate the persistence of cancer-related fatigue-like behavior.
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