Confirmation of antidepressant potential of the selective beta3 adrenoceptor agonist amibegron in an animal model of depression.

The involvement of the noradrenergic system, particularly the beta1 and beta2 receptors, in depressive disorders has been frequently shown. Recently, however, it has been shown that the beta3 receptor may also contribute since amibegron (SR58611A), a selective beta3 receptor agonist, has antidepressant-like effects. The present experiment sought to confirm the antidepressant potential of amibegron by studying its effects in an animal model of depression, the Flinders Sensitive Line (FSL) rat. The FSL rat is innately highly immobile in the forced swim test and exhibits a decrease in immobility after chronic, not acute antidepressant treatment. FSL rats were treated for 14 consecutive days with amibegron (0.3, 1.0, or 3.0 mg/kg), fluoxetine (5 mg/kg) or desipramine (5 mg/kg) as positive controls, and vehicle, while the control strain, the Flinders Resistant Line (FRL) rats, was given either vehicle or 1.0 mg/kg amibegron. About 23-25 h after the last injection the rats were tested in the forced swim test. All doses of amibegron and the two active controls, fluoxetine and desipramine, significantly reduced immobility in the FSL rats. Thus, amibegron had a selective antidepressant-like effect in this study, confirming its antidepressant potential.