Doxorubicin treatment has a biphasic effect over time on dopamine release and impulsive behavior in Wistar rats.

Doxorubicin (Dox) is a chemotherapy agent commonly used to treat multiple types of cancers and is associated with cognitive impairment. The goal of this work was to determine the effect of Dox treatment on dopamine release and uptake and behavior in rats. Rats received one dose per week of Dox (2.5 mg/kg, I.V.) and were sacrificed after two or four weeks. Dopamine release and uptake was measured in brain slices with fast-scan cyclic voltammetry (FSCV). A set of rats that received treatment also underwent behavioral testing with the 5-choice serial reaction timed task (5CSRTT) to measure degree of impulsiveness and attention throughout the course of treatment. Dopamine release and uptake increased substantially after treatment with Dox for two weeks compared to controls. After four weeks of treatment, release levels decreased to less than controls while there were no differences in uptake. Treatment of brain slices with pramipexole revealed that dopamine release was equally sensitive to autoregulation after two weeks of Dox treatment, but less sensitive after four weeks. Measurements from the 5CSRTT indicated that, while Dox did not affect attention, it increased impulsiveness after two and three weeks of treatment, but not after four weeks. Treatment with Dox for a short time may elevate dopamine system activity and increase impulsiveness, while longer administration then leads to an underactive dopamine system. To our knowledge this work demonstrates for the first time that Dox can have a biphasic neurochemical and behavioral effect.