Involvement of monoaminergic systems / pathways in the mechanism of action of the antidepressant effect of Leptadenia hastata (Pers.) decne methanol leaf extract

Depression is a mental disorder that is highly prevalent in many parts of the globe and a source of burden to patients and their families. Existing treatments for depression are far from satisfactory because many patients with depression do not respond effectively and have significant adverse effects on standard antidepressant drugs. It is vital to develop novel antidepressant from medicinal plants, which are considered a good source of drugs with fewer adverse effects. An earlier study has established the in-vivo antidepressant effect of methanol leaf extract of Leptadenia hastata. However, no scientific data on its involvement in the monoaminergic mechanism of action. This study aimed to evaluate the involvement of monoaminergic systems in the antidepressant potential of methanol leaf extract of Leptadenia hastata. The acute toxicity studies of methanol leaf extract of Leptadenia hastata (MELH) was determined using Lorke's Method. The antidepressant effect of the MELH was evaluated using the Tail Suspension Test (TST) and Open Field Test (OFT) for psychostimulant effect. The possible mechanism of antidepressant actions of the MELH was also investigated by intraperitoneal pre-treatment with adrenergic, serotonergic, dopaminergic, opioidergic and muscarinic cholinergic receptor antagonists. The intraperitonial (i.p.) median lethal dose (LD50) values were estimated to be >5000 mg/kg. Administration of standard drug, Imipramine (10 mg/kg) and MELH (250, 500, and1000 mg/kg) significantly (p<0.01) and dose-dependently decreased the duration of immobility time. However, the anti-immobility effect of the MELH was significantly (p<0.05) reversed by prazosin, cyproheptadine and naloxone, suggesting the involvement of adrenergic, serotonergic and opioidergic pathways. However, no significant interactions with dopaminergic and muscarinic cholinergic receptor antagonists were observed. This study concluded that the observed antidepressant effect in MELH is likely mediated through their interactions with adrenergic, serotonergic and opioidergic systems.