Anti-depressant effect of hesperidin in ovariectomized mice: possible involvement of dopaminergic and serotoninergic systems

Objective: This study aimed to determine anti-depressant effect of hesperidin in ovariectomized mice and its possible interaction with dopaminergic and serotoninergic systems. Materials and Methods: In experiment 1, mice were kept as control and sham groups, ovariectomized (OVX), OVX+ hesperidin (12.5 mg/kg), OVX+ hesperidin (25 mg/kg) and OVX+hesperidin (50 mg/kg). In experiment 2, mice were kept as control and sham, OVX, OVX+hesperidin (50 mg/kg), OVX+dopamine (25 mg/kg) and OVX+co-injection of hesperidin and dopamine. Experiments 3-5 were like experiment 2, except 6-OHDA (dopamine inhibitor, 100 mg/kg), fluoxetine (selective serotonin reuptake inhibitor, 5 mg/kg) and cyproheptadine (serotonergic receptor antagonist, 4 mg/kg) was injected instead of dopamine. Then, forced swimming test (FST), tail suspension test (TST) and open field test (OFT) were done. Also, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS) levels were determined. Results: According to the results, OVX increased immobility time in FST and TST tests as compared to control group (P 0.05). Hesperidin (50 mg/kg) decreased immobility time as compared to OVX group (P 0.05). Co-injection of hesperidin+dopamine decreased immobility time in TST and FST and increased number of crossing in OFT (P 0.05). Co-injection of hesperidin+6-OHDA significantly decreased antidepressant activity of the hesperidin on immobility time and decreased positive effect of the hesperidin on the number of crossing (P 0.05). Co-injection of hesperidin+Fluoxetine significantly amplified antidepressant activity of the hesperidin on immobility time and number of crossing (P 0.05). Co-injection of hesperidin+cyproheptadine decreased antidepressant activity of hesperidin on immobility time (P 0.05). Hesperidin (12.5, 25 and 50 mg/kg) decreased the MDA, while increased SOD and GPx levels in OVX mice (P 0.05). Conclusion: It is assumed that antidepressant activity of hesperidin is mediated via dopaminergic and serotoninergic receptors in OVX mice.