In light of a discovery that astroglial Kir4.1 in lateral habenula drives neuronal bursts in depression, the present disclosure provides a pharmaceutical agent and a method of use thereof for treating depression. The pharmaceutical agent can inhibit an activity of an astroglial potassium channel, and especially suppress expression or functionality of Kir4.1, in astrocytes in the lateral habenula of a subject so that bursting activity of neurons in the lateral habenula of the subject can be suppressed. The pharmaceutical agent can include a vector expressing a target nucleotide sequence in the astrocytes in the lateral habenula, whose expression is configured to suppress Kir4.1 expression by RNA interference, or to block Kir4.1 functionality by a dominant negative effect of a mutant Kir4.1 protein. The pharmaceutical agent can alternatively comprise a small molecule compound, or an active macromolecule such as an anti-Kir4.1 antibody, configured to directly inhibit the astroglial potassium channel activity.