TY - JOUR
T1 - Associative learning contributes to the persistence of fatigue-like behavior in male mice in a model of cancer survivorship
AU - Vichaya, Elisabeth G.
AU - Darpolor, Josephine K.
AU - Gross, Phillip S.
AU - Molkentine, Jessica M.
AU - Vermeer, Daniel W.
AU - Vermeer, Paola D.
AU - Lee, John H.
AU - Taniguchi, Cullen M.
AU - Dantzer, Robert
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2023/1
Y1 - 2023/1
N2 - 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 variations 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 provide the first demonstration that associative processes can modulate the persistence of cancer-related fatigue-like behavior.
AB - 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 variations 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 provide the first demonstration that associative processes can modulate the persistence of cancer-related fatigue-like behavior.
KW - Associative learning
KW - Cancer
KW - Chemoradiation
KW - Conditioned responses
KW - Fatigue
KW - Survivorship
UR - http://www.scopus.com/inward/record.url?scp=85141311032&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141311032&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2022.10.018
DO - 10.1016/j.bbi.2022.10.018
M3 - Article
C2 - 36323360
AN - SCOPUS:85141311032
SN - 0889-1591
VL - 107
SP - 296
EP - 304
JO - Brain, behavior, and immunity
JF - Brain, behavior, and immunity
ER -