Oleuropein Reverses Repeated Corticosterone-Induced Depressive-Like Behavior in mice: Evidence of Modulating Effect on Biogenic Amines

Abstract

Depression is still one of challenging, and widely encountered disorders with complex etiology. The role of healthy diet and olive oil in ameliorating depression has been claimed. This study was designed to explore the effects of oleuropein; the main constituent of olive oil; on depression-like behaviors that are induced by repeated administration of corticosterone (40 mg/kg, i.p.), once a day for 21 days, in mice. Oleuropein (8, 16, and 32 mg/kg, i.p.) or fluoxetine (20 mg/kg, positive control, i.p.1) was administered 30 minutes prior to corticosterone injection. Sucrose consumption test, open-field test (OFT), tail suspension test (TST), and forced swimming test (FST) were performed. Reduced Glutathione (GSH), lipid peroxidation, and biogenic amines; serotonin, dopamine, and nor-epinephrine; levels were also analyzed in brain homogenates. Corticosterone treatment induced depression-like behaviors, it increased immobility time in the TST, OFT, and FST, decreased the number of movements in OFT, and decreased sucrose consumption. Corticosterone effect was associated with depletion of reduced glutathione and increase of lipid peroxidation, in addition to modification of biogenic amines; decreased serotonin and dopamine. Oleuropein or fluoxetine administration counteracted corticosterone-induced changes. In conclusion, oleuropein showed a promising antidepressant activity, that is evident by improving corticosterone-induced depression-like behaviors, and normalizing levels of biogenic amines.

Figure 1

Effects of different doses of oleuropein on immobility time in chronic Cort-induced depression model. (a) Tail Suspension Test (TST) and (b) Forced Swimming Test (FST) in different animal groups. Each bar represents the mean of 6 rats + SEM. a: significant compared to the control group; b: significant compared to the Cort group; c: significant compared to Cort + Fluoxetine group; d: significant compared to Cort + oleuropein (8 mg/kg) group. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.

Figure 2

Effects of different doses of oleuropein on chronic Cort-induced depression model. (a) Immobility Time in Open Field Test (OFT), (b) Number of Movements in Open Field Test (OFT), and (c) Sucrose Consumption % in Sucrose Preference Test in different animal groups. Each bar represents the mean of 6 rats + SEM. a: significant compared to the control group; b: significant compared to the Cort group; c: significant compared to Cort + Fluoxetine group; d: significant compared to Cort + oleuropein (8 mg/kg) group. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.

Figure 3

Effects of different doses of oleuropein on oxidative stress-related parameters in chronic Cort-induced depression model. (a) Reduced Glutathione (GSH); u Mol/g tissue protein; and (b) Thiobarbituric Acid Reactive Substances (TBARS); u Mol/g tissue protein in different animal groups. Each bar represents the mean of 6 rats + SEM. a: significant compared to the control group; b: significant compared to the Cort group; c: significant compared to Cort + Fluoxetine group; d: significant compared to Cort + oleuropein (8 mg/kg) group. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.

Figure 4

Effects of different doses of oleuropein on brain neurotransmitters’ level in chronic Cort-induced depression model in mice. (a) Brain Serotonin (5-HT) Level (ng/ml), (b) Brain Dopamine Level (ng/ml), and (c) Brain Norepinephrine Level (ng/ml) in different animal groups. Each bar represents the mean of 6 rats + SEM. a: significant compared to the control group; b: significant compared to the Cort group; c: significant compared to Cort + Fluoxetine group; d: significant compared to Cort + oleuropein (8 mg/kg) group. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.