Objectives/purpose:
The efficacy of chemotherapy is often limited by its side effects, including fatigue, cognitive impairment, and emotional distress. Converging evidence suggests that chemotherapy may disrupt effort-based decision-making (EBDM), a cognitive process that integrates motivational and executive control mechanisms. This study aimed to examine the effects of the chemotherapeutic agent doxorubicin (DOX) on physical and cognitive EBDM in rats.
Sample and setting:
Female Sprague-Dawley Rats received DOX (2 mg/kg) or vehicle once weekly for four weeks.
Procedures:
General physical activity was assessed with voluntary wheel running as an index of fatigue. Physical EBDM was assessed with a T-maze concurrent choice paradigm, in which rats chose between climbing a 30-cm barrier for a high reward (HR) or entering a barrier-free arm for a low reward. Cognitive EBDM was assessed using a choice task involving lever pressing under differential reinforcement of low rates (DRL) schedules, which required high or low levels of response inhibition.
Results:
DOX treatment transiently reduced voluntary activity but did not impair either physical or cognitive EBDM. In the T-maze, DOX-treated rats showed greater persistence than vehicle-treated rats in choosing the HR arm even after reward reduction. In the cognitive effort task, DOX-treated rats displayed greater perseveration by continuing to choose the HR lever despite increased inhibition demands.
Conclusions and clinical implications:
These findings suggest that although DOX did not affect EBDM, it may impair goal-directed behaviour by promoting habitual responding and reducing sensitivity to cognitive effort. Our study implicates that subtle impairments in behavioural flexibility and effort monitoring may mask the seemingly intact motivational capacity exhibited by cancer survivors.