Doxorubicin dose-dependently induces cognitive impairment and anxiety in conditioned passive avoidance and elevated plus-maze tests in rats

Background. Cognitive impairment and anxiety are common side effects of anticancer chemotherapy, particularly with doxorubicin (DOX). Therefore, there is a need to develop experimental models to assess DOX-induced dose-dependent impairments in cognitive function and emotional behavior.

The aim — study of the dose-dependent effect of the anthracycline antitumor drug doxorubicin (DOX) on the formation and reproduction of a memory trace, anxiety, and motor responses in experiments on healthy sexually mature rats.

Materials and methods. The experiments were performed on outbred male rats that were administered DOX (2.0 and 3.0 mg/kg, intraperitoneally) once a week for 4 weeks. To record exploratory behavior, assess motor reactions and anxiety behavior, the following tests were used: “open field”, “rotary rod”, “horizontal bar” and “elevated plus maze” (EPM). The influence of DOX on the processes of learning and reproduction of a memory trace was studied in the test of the conditioned reflex of passive avoidance (CPAR).

Results. DOX at doses of 2 and 3 mg/kg did not affect rat behavior in the open field test and did not impair motor coordination in the rotarod and horizontal crossbar tests. In the EPM test, DOX (3 mg/kg) increased anxiety response. DOX at a dose of 2 mg/kg, which does not induce anxiety, did not affect rat learning in the CPAR test. However, after 24 hours and 7 days, DOX (2 mg/kg) reduced the latency time of entry into the dark compartment of the setup compared to the control, which indicates a disruption in the reproduction of the CPAR.

Conclusion. The obtained data confirm the validity of using DOX (2 mg/kg) for modeling cognitive impairment and anxiety at the stage of preclinical study of biologically active substances.

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