Various studies have shown that calcium channel blockers (CCB) affect the release of central neurotransmitters including noradrenaline (NA) and 5-hydroxytryptamine (5-HT), which are involved in depression. The behavioural despair test was used to investigate the effect of CCB on depression. The mice were treated acutely with CCB. Verapamil (5, 10, 20, and 40 mgkg⁻¹, i.p.) and diltiazem (10, 20, and 40mgkg⁻¹ , i.p.) produced a dose-dependent increase in immobility time, indicating the facilitation of depression, while nifedipine (12.5, 25, and 50 mgkg⁻¹, i.p.) significantly decreased the immobility time, indicating an antidepressant activity. Verapamil ( 40 mgkg⁻¹, i.p.) and diltiazem ( 40 mgkg⁻¹, i.p.) blocked the antidepressant effect of desipramine, clomipramine, mianserin, and tranylcypromine, indicating the involvement of various mechanisms in the facilitatory effect of verapamil and diltiazem on depression. The antidepressant effect of nifedipine may be attributed to the blockade of presynaptic α -2-receptors (autoreceptors), as nifedipine blocked the clonidine-induced facilitation of depression.