5-Fluorouracil impairs attention and dopamine release in rats

Publication date: Available online 7 January 2019

Source: Behavioural Brain Research

Author(s): David P. Jarmolowicz, Rachel Gehringer, Shea M. Lemley, Michael J. Sofis, Sam Kaplan, Michael A. Johnson

Abstract

Chemotherapy related cognitive impairment (CTRC; "chemobrain") is a syndrome that is associated with the impairment of various aspects of cognition, including executive function, processing speed, and multitasking. The role of neurotransmitter release in the expression of cognitive impairments is not well known. In this work we employed a newly developed behavioral paradigm to measure attentional shifting, a fundamental component of executive function, in rats treated with 5-fluorouracil (5-FU), a commonly used cancer chemotherapy agent. We found that one and two weeks of 5-FU treatment significantly impaired attentional shifting compared to baseline, while saline treatment had no effect. Post-mortem analysis of these rats revealed that 5-FU caused a significant overall decrease in dopamine release as well. Collectively, these results demonstrate the feasibility of our attentional shifting paradigm for evaluating the cognitive effects of chemotherapy treatment. Moreover, these results support the need for additional studies to determine if impaired dopamine release plays a role in chemobrain.

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