Edaravone presents antidepressant-like activity in corticosterone model of depression in mice with possible role of Fkbp5, Comt, Adora1 and Slc6a15 genes

Abstract

Chronic exposure to environmental-like stress leads to dysregulation of hypothalamic–pituitary–adrenal (HPA) axis and to appearance of oxidative stress, which is implicated in the development of depression-like behaviour. Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) exhibits a neuroprotective effect attributed to the potent free radical scavenging. This study was designed to assess antidepressant-like activity of edaravone based on behavioural tests in the animal model of depression. Furthermore, to elucidate its mechanisms, the expression of Fkbp5, Comt, Adora and Slc6a15 genes involved in turnover of neurotransmitters was analysed. In order to evaluate the antioxidant features of edaravone, DNA's oxidative damage was determined. The mice were injected subcutaneously (sc) with 40 mg/kg corticosterone, chronically for 21 days. Paroxetine (10 mg/kg) (a selective serotonin reuptake inhibitor) and edaravone (10 mg/kg) were administered separately (ip) 30 min prior to the corticosterone injection. After 21-days of treatment with respective drugs, the mice were decapitated and the prefrontal cortex was rapidly dissected and used for determination of DNA's oxidative damage and the real-time PCR analysis. Edaravone ameliorated behavioural impairments in sucrose preference test (SPT) and forced swim test (FST). A possible role in Fkbp5, Comt, Adora1 and Slc6a15 genes' expression in mediating this effect is postulated. Both edaravone and paroxetine have no effect on corticosterone-induced DNA's oxidative damage.