Effect of dextromethorphan in the mouse forced swim and tail suspension tests: Evidence for involvement of the alpha receptors

Depression is a state of low mood that can seriously affect the quality of life of society. Therefore, finding new antidepressant agents with high efficacy is needed. Dextromethorphan (DXM) is an antitussive drug that has a potential effect on treating mood disorders, especially depression. However, because of limited data that relies on a few experimental animal studies mechanisms of action are yet not clear. The present study investigated the DXM effect in the forced swimming (FST) and tail suspension (TST) tests in mice and also the potential influence of the noradrenergic system in this effect. DXM (30 mg/kg, intraperitoneal (i.p.)) significantly decreased the immobility times in FST (P < 0.001) and TST (P < 0.01) comparable with positive controls, imipramine (IMI) 10 mg/kg and fluoxetine (20 mg/kg). Nevertheless, the number of crossings in the openfield test was not affected. The pretreatment with prazosin (1 mg/kg, i.p.; alpha 1-adrenoceptor antagonist) or yohimbine (1 mg/kg, i.p.; alpha 2-adrenoceptor antagonist) prevented the antidepressant effect of DXM (30 mg/kg, i.p). Moreover, the administration of a sub-effective dose of phenylephrine (5 mg/kg, i.p.; alpha 1-adrenoceptor agonist) or clonidine (0.06 mg/kg, i.p.; alpha 2-adrenoceptor agonist) potentiated the sub-effective dose of DXM (3 mg/kg, i.p.) in the FST and TST. The pretreatment with propranolol (5 mg/kg, i.p.; beta-adrenoceptor antagonist) did not reverse the antidepressant-like effect of DXM. Thus, the present study suggests that the antidepressant-like effect of DXM may be partially related to alpha 1/alpha 2 adrenoceptors