Assessment of the Antidepressant Activity and Monoaminergic Mechanisms of Aqueous Extract of Spondias mombin Leaves in Behavioural Models of Depression

Depression is a leading cause of disability in Nigeria, with prevalence estimated at 22% in the general adult population across urban and peri-urban settings in the South West and South East zones. Access to formal psychiatric care and pharmacotherapy remains severely constrained for most Nigerians, driving reliance on traditional botanical treatments. Spondias mombin, the hog plum or iyeye, is used by traditional healers in Ogun, Ondo, and Cross River States for conditions characterised by psychological distress and mood disturbance. This study investigates the antidepressant activity and monoaminergic mechanisms of aqueous Spondias mombin leaf extract using validated rodent behavioural depression models. The forced swim test (FST), tail suspension test (TST), and open field locomotor activity test were employed to characterise antidepressant-like behaviour. Dose groups received extract at 100, 200, and 400 mg/kg, with fluoxetine (10 mg/kg) and imipramine (15 mg/kg) as reference antidepressants. Monoaminergic mechanism analysis employed pharmacological antagonism with p-chlorophenylalanine (serotonin depletor), reserpine, and prazosin to delineate serotonergic, catecholaminergic, and adrenergic contributions. Synaptosomal monoamine reuptake inhibition assays were performed for serotonin, noradrenaline, and dopamine. Extract at 200 and 400 mg/kg significantly reduced immobility in FST and TST without altering locomotor activity. Serotonin depletion attenuated the antidepressant effect by 67%, implicating serotonergic pathways as primary mediators. Vitexin and quercetin were identified as the most pharmacologically relevant phytoconstituents. These findings justify further development of Spondias mombin as a plant-based antidepressant candidate. Keywords: Spondias mombin, antidepressant, monoaminergic, serotonin, forced swim test