Risperidone, an atypical antipsychotic enhances the antidepressant-like effect of venlafaxine or fluoxetine: Possible involvement of alpha-2 adrenergic receptors

Clinical studies have reported the beneficial outcome of addition of lower doses of risperidone to antidepressant therapy specifically with selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depression. The present study, therefore, examined the beneficial effect, if any, of addition of risperidone (an atypical antipsychotic) to the antidepressant-like effect of venlafaxine (dual reuptake inhibitors of both serotonin and norepinephrine, SNRI) or fluoxetine (SSRI) in Porsolt's Forced Swim Test (FST) using male laca mice. Attempts have been made to study the involvement of alpha-2 adrenergic receptors in the mechanism of action. Immobility period was recorded for a period of 6 min. Venlafaxine (4 and 8 mg/kg, i.p.) or fluoxetine (10 and 20 mg/kg, i.p.) inhibited the immobility period in mice. Addition of risperidone (0.1 mg/kg, i.p.) potentiated the anti-immobility effect of either venlafaxine (4 and 8 mg/kg, i.p.) or fluoxetine (10 and 20 mg/kg, i.p.) in mouse FST. Furthermore, the anti-immobility effect of combination of risperidone (0.1 mg/kg, i.p) plus venlafaxine (4 mg/kg, i.p.) or fluoxetine (10 mg/kg, i.p.) was potentiated by the addition of yohimbine (2 mg/kg, i.p.), an alpha-2 adrenoceptors antagonist. The results of the present study suggest that the beneficial consequences of addition of risperidone with venlafaxine or fluoxetine in mouse forced swim test may involve alpha-2 adrenergic receptors.