Anti-depressant effect of Betaine mediates via nitrergic and serotoninergic systems in ovariectomized mice

This study aimed to determine the anti-depressant effect of betaine (BT) in ovariectomized mice and its possible interaction with nitrergic and serotoninergic systems. In experiment 1, the mice were divided into control and sham groups, ovariectomy (OVX), OVX+BT (12.5mg/kg), OVX+BT (25 mg/kg), and OVX+BT (50mg/kg) groups. In experiment 2, the mice were assigned into control and sham, OVX, OVX+BT (50mg/kg), OVX+L-NAME (10 mg/kg), as well as OVX+injection of the BT and L-NAME. Experiments 3-5 were similar to experiment 2, except for L-Arginine (50 mg/kg), Fluoxetine (5 mg/kg), and Cyproheptadine (4 mg/kg) that were injected instead of the L-NAME. Subsequently, forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed in this study. Moreover, this study determined serum Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione peroxidase (GPx), and total antioxidant status levels. According to the findings, OVX increased immobility time, compared to the control group (P<0.05). In addition, BT (50mg/kg) decreased depression-induced immobility time, compared to the OVX group (P<0.05). The co-injection of the BT+L-NAME decreased depression-induced immobility time in TST and FST, followed by an increase in the number of crossing in OFT(P<0.05).Moreover, the co-injection of the BT+L-Arginine significantly diminished the antidepressant activity of BT on immobility time and decreased positive effect of BT on the number of crossing (P<0.05). The co-injection of the BT+Fluoxetine significantly amplified the antidepressant activity of BT on immobility time and number of crossing (P<0.05). Furthermore, the co-injection of the BT+Cyproheptadine decreased antidepressant activity of BT on immobility time and number of crossing (P<0.05). The BT (25 and 50mg/kg) reduced the MDA; however, it elevated SOD and GPx levels in OVX mice (P<0.05). It seems that antidepressant activity of BT mediates via nitrergic and serotoninergic systems in OVX mice.