Anxiolytic and antidepressant effects of Ziziphus mucronata hydromethanolic extract in male rats exposed to unpredictable chronic mild stress: Possible mechanisms of actions

Ethnopharmacological relevance: Ziziphus mucronata (ZM) is used traditionally in the treatment of mood and depression. However, no existing scientific data is confirming this traditional claim.

Aim of the study: The present study was planned to investigate the anxiolytic and antidepressant-like effects of this plant in a stressed-induced depression model in rats.

Materials and methods: Depressive-like behaviors were induced by exposing rats to different stress paradigms daily for 30 days. A sucrose preference test was performed to assess anhedonia in rats. Anxiety and depression-related behavior were assessed. The oxidative parameters (lipid peroxidation, SOD and catalase activities) were evaluated. Pindolol and Flumazenil were also used to assess the mechanism of action of ZM extract.

Results: The results showed that chronic administration of ZM (150, 300, and 600 mg/kg, p.o., 30 days) and imipramine treatment (20 mg/kg, p.o, 30 days) remarkably (P < 0.05) reversed the UCMS-induced behavioral changes observed in stress vehicle treated rats by reducing sucrose preference, decreased the immobility period in the FST and latency in NSF. Besides, ZM (300 and 600 mg/kg, p.o., 30 days) raised the percentages of time spent and number of open arms entries as well as the number of transitions. Also, ZM (300 mg/kg, (P < 0.05) decreased lipid peroxidation and increased both SOD and catalase activities (300 and 600 mg/kg, (P < 0.05)). These aforementioned behavioral indices were also completely nullified by pindolol a β-adrenoceptors blocker and 5-HT 1A/1B receptor antagonist but not by flumazenil, a benzodiazepine receptors antagonist.

Conclusion: ZM improved symptoms of anxiety and depression in behavioral despair paradigm in chronically stressed rats. The observed effects could be due to its capacities to restore the antioxidant status, and probably the modulation of monoamines transmissions.

Keywords: Anhedonia; Antioxidant; Chronic mild stress; Monoamines; Ziziphus mucronata.