The role of serotonergic and catecholaminergic systems for possible antidepressant activity of apigenin

BACKGROUND AND OBJECTIVE: Although, the anti-depressant like effects of apigenin (APG) are documented in the literature, the underlying mechanism for exerting such an effect is still not clear. In this research, an attempt was made to determine the possible role of APG for antidepressant activity through serotonergic and catecholaminergic systems using standardized animal models. MATERIALS AND METHODS: The antidepressant property of APG was determine by involving tail suspension (TST) and modified forced swimming tests (MFST). The effect of APG was evaluated at 25 and 50 mg/kg. In mechanistic models, animals were pretreated with catecholaminergic and serotonergic antagonists prior to administration of APG. The results obtained were statistically analyzed to determine the level of significance. RESULTS: The period of immobility in both models (TST and MFST) was significantly reduced by APG (25 and 50 mg/kg). The best therapetuic dose of APG (50 mg/kg) was selected for the mechanistic study. The anti-immobility effect of APG declined to a significant extent upon pretreatment with catecholaminergic antagonists (α-methyl-para-tyrosine methyl ester; SCH 23390; sulpiride; phentolamine) and serotonergic inhibitors (p-clorophenylalanine-methyl-ester; ondansetron) in both TST and MFST models. The antidepressant benefits of apigenin were only modestly reversed when rats were given propranolol. CONCLUSIONS: The findings suggest that APG's antidepressant effect is mediated by the α-adrenergic, dopaminergic and 5-HT3 serotonergic receptors.