Effect of Hesperetin on the Antidepressant Activity of Electroconvulsive Therapy in an Enforced Reserpine Model of Depression in Male Rats

Background: Depression is a common and debilitating disorder of the brain. Many pharmacological therapies, including many plant components (such as flavonoids), are used to treat depression. Electroconvulsive therapy (ECT) is a useful method for depressed patients who do not respond to medication. However, this method has some side effects. Hence, investigators have tried to improve ECT’s positive points by diminishing its side effects. Objectives: We investigated the effect of hesperetin (a flavonoid component) on the antidepressant activity of ECT in an enforced reserpine model of depression in male rats. Methods: Eighty male rats (230 - 250 g) were randomly divided into control, ECT + reserpine (Res), Res + hesperetin (Hes; 10 or 20 mg/kg), Res + ECT, and Res + ECT + Hes (10 or 20 mg/kg) groups. The effects of hesperetin were evaluated by the forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), elevated plus maze test (EPMT), as well as by measurement of the brain-derived neurotrophic factor (BDNF) and oxidative stress biomarkers [ie, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH)] in the prefrontal cortex area. Results: The outcomes of the behavioral experiments showed that Hes + ECT treatment could raise the percentage of open arm entrance in EPMT, anhedonia in SPT, and decrease immobilization time in FST compared to the groups treated with ECT (P < 0.05) or hesperetin alone. Our biochemical research also illustrated a significant reduction in MDA in the groups treated with ECT + Hes (10 or 20 mg/kg; P < 0.01 and P < 0.001) and ECT or hesperetin, as well as a significant increase in GSH, SOD, and BDNF in the ECT + Hes (20 mg/kg) animal group (P < 0.001). Conclusions: In depressed rats, the ECT linked to the application of hesperetin could significantly elevate BDNF, GSH, and SOD reduction in depressed male rats.