New therapeutic strategies against depression, with less side effects and thus greater efficacy in larger proportion of depressed patients, are needed. Amibegron (SR58611A) is the first selective beta 3 adrenergic agent that has been shown to possess a profile of antidepressant activity in rodents. to investigate the involvement of serotonin receptors in the effects of amibegron, we used the serotonin 5HT1A receptor antagonist WAY-100635 (WAY) or serotonin 5HT2A-2C receptor antagonist ketanserin or serotonin 5HT3 receptor antagonist ondansetron in mice forced swimming test (FST). The locomotor activity was evaluated by measuring the total distance moved in the apparatus and the speed of the animals in the open field test. Imipramine (30 mg/kg) significantly reduced immobility time compared to vehicle-treated group while amibegron (5 and 10 mg/kg) dose dependently reduced immobility time in the FST. WAY(0.1 mg/kg), ondansetron (1 mg/kg), ketanserin(5 mg/kg) had no effect on immobility time in naive mice while all of the drugs partially and significantly reversed amibegron (10 mg/kg) induced decreasement in the immobility time in FST. None of the drugs alter locomotor activity in the open field test. The antidepressant-like effect of amibegron in the FST seems to be mediated by an interaction with serotonin 5-HT1A, serotonin 5-HT2A-2C and serotonin 5-HT3 receptors. (C) 2013 Elsevier Inc. All rights reserved.