Objective: Regarding the involvement of potassium and calcium channel and/ or GABA_B receptors in the pathogenesis of depression, the effects of glibenclamide (potassium channel blocker), amlodipine (calcium channel blocker) and baclofen (GABA_B agonist) on the efficacy of the two antidepressant drugs (amitriptyline and fluoxetine) were investigated in forced swimming test in mice as a model for depression. 
Method: This investigation is an experimental study. Forced swimming test was applied as a model for depression; the immobility time was considered as an indicator of depression of animal. In the present study the effects of glibenclamide, amlodipine and baclofen on antidepressant effects of amitriptyline and fluoxetine were evaluated. Next, the effects of glibenclamide, amlodipine and baclofen on antidepressant effects of amitriptyline and fluoxetine were studied. 
Results: Our data showed that neither glibenclamide nor amlodipine altered the immobility time and neither influenced the antidepressant response of amitriptyline and fluoxetine. In the second set of experiments, administration of a higher dose of baclofen decreased immobility time, while low doses of baclofen did not have a significant effect. Furthermore, administration of different doses of baclofen enhanced the antidepressant effects induced by amitriptyline, while coadministration of baclofen and fluoxetine decreased the antidepressant effects of fluoxetine. 
Conclusion: GABA_B receptors play a dual role in the antidepressant responses of amitriptyline and fluoxetine.