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In a previous study conducted by our group, riparin II (ripII) isolated from the green fruit of Aniba riparia presented antianxiety effects in mice. This study investigates a possible antidepressant activity of rip II using two predictive tests for antidepressant activity in rodents: the forced swimming test (FST) and tail suspension test (TST). Additionally, the mechanisms involved in the antidepressant-like effect in mice were also assessed. Rip II was acute administered by intraperitoneal (i.p.) and oral (p.o) routes to male mice at doses of 25 and 50 mg/kg. Results showed that ripII at both tested doses and administration routes produced a significant decrease of immobility time in FST and TST. The pretreatment of mice with prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), SCH23390 (15 μg/kg, i.p., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), p-chlorophenylalanine (100 mg/kg, an inhibitor of serotonin synthesis), or NAN-190 (0.5 mg/kg, a serotonin 5-HT1A receptor antagonist) completely blocked the anti-immobility effects elicited by riparin II (50 mg/kg, p.o.) in the FST. This study indicates that riparin II produces significant antidepressant-like activity in the forced swimming and TSTs, and this effect seems to be dependent on its interaction with noradrenergic, dopaminergic, and serotonergic systems.