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However, the effects of chemotherapy on motivational and decision-making processes related to fatigue remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to examine the effects of the chemotherapeutic agent doxorubicin (DOX) on physical and cognitive effort-based decision-making using novel behavioural procedures in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female Sprague-Dawley rats received DOX (2\u00a0mg\/kg, i.p.) or vehicle once weekly for four weeks. Voluntary wheel running was used to assess general physical activity. Physical effort-based decision-making 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 effort-based decision-making was assessed using a choice task involving lever pressing under differential reinforcement of low-rate schedules requiring different levels of response inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DOX transiently reduced voluntary activity but did not impair either physical or cognitive effort expenditure. In the T-maze, DOX-treated rats showed greater perseveration than vehicle-treated rats by continuing to choose the HR arm even after reward reduction. In the cognitive effort task, DOX-treated rats similarly perseverated by continuing to choose the HR lever despite increased inhibition demands.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that while DOX did not directly impair effort-based decision-making, it may disrupt executive function processes, particularly behavioural flexibility and working memory, which are critical for adapting behaviour to changing task contingencies and translating effort costs into goal-directed behaviour.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-026-07098-5","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:27:28Z","timestamp":1780662448000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of chemotherapy on cognitive and physical effort-based decision-making tasks in rats"],"prefix":"10.1007","author":[{"given":"Weiye","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9408-2232","authenticated-orcid":false,"given":"Ian N.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"7098_CR1","doi-asserted-by":"publisher","first-page":"1251917","DOI":"10.3389\/fphar.2023.1251917","volume":"14","author":"AH Alhowail","year":"2023","unstructured":"Alhowail AH, Aldubayan MA (2023) Doxorubicin impairs cognitive function by upregulating AMPAR and NMDAR subunit expression and increasing neuroinflammation, oxidative stress, and apoptosis in the brain. 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