Antidepressant-Like Effect of the Leaves of Pseudospondias microcarpa in Mice: Evidence for the Involvement of the Serotoninergic System, NMDA Receptor Complex, and Nitric Oxide Pathway

Abstract

Depression continues to be a major global health problem. Although antidepressants are used for its treatment, efficacy is often inconsistent. Thus, the search for alternative therapeutic medicines for its treatment is still important. In this study, the antidepressant-like effect of Pseudospondias microcarpa extract (30–300mg kg−1, p.o.) was investigated in two predictive models of depression—forced swimming test and tail suspension test in mice.Additionally, the mechanism(s) of action involvedwere assessed. Acute treatment with the extract dose dependently reduced immobility of mice in bothmodels.Theantidepressant-like effect of the extract (100mg kg−1, p.o.) was blocked by 𝑝-chlorophenylalanine and cyproheptadine but not prazosin, propranolol, or yohimbine. Concomitant administration of d-cycloserine and the extract potentiated the anti-immobility effect. In contrast, d-serine, a full agonist of glycine/NMDA receptors, abolished the effects. Anti-immobility effects of PME were prevented by pretreatment of mice with L-arginine (750mg kg−1, i.p.) and sildenafil (5mg kg−1, i.p.).On the contrary, pretreatment of mice with L-NAME (30mg kg−1, i.p.) or methylene blue (10mg kg−1, i.p.) potentiated its effects. The extract produces an antidepressant-like effect in the FST and TST that is dependent on the serotoninergic system, NMDA receptor complex, and the nitric oxide pathway.