Esculetin improves chemotherapy-induced impaired anxiety-depression-like behaviors and learning activity

INTRODUCTION: This study aimed to assess the neuroprotective effectiveness of esculetin in preventing cognitive and emotional impairments caused by chemotherapy.
METHODS: In order to cause cognitive impairment in mice, a single intraperitoneal dosage of methotrexate (Mtx) at a concentration of 40 mg/kg was administered. Esculetin (Elt) was administered orally at a daily dose of 40 mg/kg one week before the Mtx injection. The locomotor activity was assessed using the Pole (PT) and open field (OF) tests. Anxiety-like behaviors were evaluated using the open field and elevated plus maze (EPM) tests. Depression-like behaviors were assessed using the tail suspension test (TST). Learning and memory activity was evaluated using the novel object recognition test (NOR).
RESULTS: Mtx did not affect the locomotor activities of mice, but anxiety-like behaviors were found to be increased in the OF and EPM tests. It also increased the duration of immobility in the TST, causing a negative discrimination index in the NOR. Elt alleviated anxiety and depression-like behaviors generated by Mtx and enhanced cognitive function related to learning and memory. Elt significantly increased the time spent in the center zone in the OF test, the total time spent in the open arms in the EPM, and the immobility time in the TST. Moreover, it improved the discrimination index in NOR, which had been reduced by Mtx.
DISCUSSION AND CONCLUSION: Administering a single dose of Mtx at 40 mg/kg resulted in increased anxiety and depression-like behaviors, impaired learning and memory functions. Besides that, supplementing with Elt significantly mitigated the neurological impairments caused by Mtx.