Antidepressant-Like Effect of the Leaves ofPseudospondias microcarpain 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 (30–300 mg 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 involved were assessed. Acute treatment with the extract dose dependently reduced immobility of mice in both models. The antidepressant-like effect of the extract (100 mg 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 (750 mg kg−1, i.p.) and sildenafil (5 mg kg−1, i.p.). On the contrary, pretreatment of mice with L-NAME (30 mg kg−1, i.p.) or methylene blue (10 mg 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.

Neurobehavioural Mechanism of Antidepressant Effect of Methanol Stem Bark Extract of Adansonia digitata (Linn) in Tail Suspension Test in Mice

“…In this study, the anti-immobility effect of MSAD was abolished by prasozin (an α 1 -adrenoceptor antagonist) (Figure 2 Panel A) and yohimbine (an α 2 -adrenoceptor antagonist) ( Figure 2 Panel B) suggesting that MSAD might be acting via interaction with α 1 -and α 2 -adrenoceptors. This observation is in line with previous reports of medicinal plants acting via these mechanisms [37,46].…”

“…MSAD shortened immobility time in TST suggesting an antidepressant-like effect. This finding is in line with previous findings of agents that shortened immobility time in TST, which were suggested to have antidepressant-like effect in TST [37,46]. Of particular interest, is the dose-dependent increase in antidepressant effect of MSAD reported by earlier researchers [47] with highest antidepressant effect exhibited at 1000 mg/kg, per oral in their study, but in our study, the lowest tested dose of 200 mg/kg, per oral of MSAD showed the highest antidepressant effect.…”

“…This experimental finding is in line with earlier experimental findings of the medicinal agents whose antidepressant-like effects were reversed by sulpiride and suggested to be acting via dopaminergic pathways [38,46]. Inhibition of 5-HT 2 receptors plays an important role in the antidepressant effect of the antidepressant agent in TST [37]. In this study, pretreatment of mice with cyproheptadine (a 5-HT 2 receptor antagonist), did not reverse the antidepressant-like effect of MSAD, indicating that its antidepressant-like effect, may not be mediated via 5-HT 2 receptor neurotransmissions.…”

“…Previous reports have indicated that acute administration of α 1 -adrenergic receptor antagonist and α 2 -adrenergic receptor antagonists abolished the antidepressant effect of antidepressant agents in TST [37,46]. In this study, the anti-immobility effect of MSAD was abolished by prasozin (an α 1 -adrenoceptor antagonist) (Figure 2 Panel A) and yohimbine (an α 2 -adrenoceptor antagonist) ( Figure 2 Panel B) suggesting that MSAD might be acting via interaction with α 1 -and α 2 -adrenoceptors.…”

“…Group I: mice received normal saline p.o (10 mL/kg); Groups II: mice received 200 mg/kg, p.o of MSAD; Group III & IV mice were pretreated with L-Arginine [750 mg/kg, i.p., a precursor of nitric oxide (NO)]and methylene blue [10 mg/kg, i.p., an inhibitor of nitric oxide synthase and an inhibitor of soluble guanylate cyclase (sGC)] respectively 15 min before MSAD; Group V: mice orally treated with MSAD, 30 min before L-NNA (0.3 mg/kg, i.p., a competitive inhibitor of NO synthase with selectivity for the neuronal and endothelial isoforms of the enzyme). One hour after oral administration of normal saline or extract in Groups I & II, 45 min after MSAD ingestion in Group III & IV[37] and 30 min after MSAD administration in Group V, mice were tested on TST[38].…”