Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems.

We have recently shown that the hexanic extract from leaves of Schinus molle produces antidepressant-like effects in the tail suspension test in mice. This study investigated the antidepressant-like effect of the ethanolic extract from aerial part of S. molle in the forced swimming test and tail suspension test in mice, two predictive models of depression. Moreover, we investigated the antidepressant potential of rutin, a flavonoid isolated from the ethanolic extract of this plant and the influence of the pretreatment with the inhibitors of serotonin or noradrenaline synthesis, p-chlorophenylalanine methyl ester (PCPA) and alpha-methyl-p-tyrosine (AMPT), respectively in the antidepressant-like effect of this flavonoid. The administration of the ethanolic extract produced a reduction in the immobility time in the tail suspension test (dose range 600-1000 mg/kg, p.o.), but not in the forced swimming test. It also produced a reduction in the ambulation in the open-field test in mice not previously habituated to the arena, but no effect in the locomotor activity in mice previously habituated to the open-field. The administration of rutin reduced the immobility time in the tail suspension test (0.3-3 mg/kg, p.o.), but not in the forced swimming test, without producing alteration in the locomotor activity. In addition, pretreatment of mice with PCPA (100 mg/kg, i.p., for 4 consecutive days) or AMPT (100 mg/kg, i.p.) prevented the anti-immobility effect of rutin (0.3 mg/kg, p.o.) in the tail suspension test. The results firstly indicated the antidepressant-like effect of the ethanolic extract of S. molle in the tail suspension test may be dependent on the presence of rutin that likely exerts its antidepressant-like effect by increasing the availability of serotonin and noradrenaline in the synaptic cleft.