Antidepressant Effect of Hydroalcoholic Extract of <i>Citrus medica</i> Fruit in Mice: Possible Role of Nitric Oxide

: Lipopolysaccharide (LPS) has been shown to cause depression by activating microglia and inducing pro-inflammatory factors in the brain. Citrus medica (CM) is a plant with known therapeutic effects. In this study, depression was induced in mice using intraperitoneal (IP) LPS (1 mg/kg). Two days later, behavioral tests were conducted. Mice were divided into nine groups of seven, including the control group, LPS group, CM extract groups (at different doses), L-arginine (L-Arg, alone and with an effective 1.dose of CM extract), aminoguanidine (AG, with an ineffective dose of CM extract), L-NAME (with an ineffective dose of CM extract), and fluoxetine 30 minutes before LPS. In the behavioral tests, the duration of immobility in mice treated with CM extract was reduced compared to the control and LPS groups. Treatment with L-Arg increased the duration of immobility, which was reversed by CM extract. The concurrent administration of L-NAME and AG with CM extract demonstrated synergistic antidepressant effects.