Abstract Classical antidepressant therapy has mainly used selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), but tianeptine appears to possess effects on 5-hydroxytryptamine (5-HT, serotonin) levels in the synaptic cleft contradictory to those of SSRIs. The mechanism behind its antidepressant effects is still unclear. The effect of tianeptine on the electrophysiological characteristics of neurons in the dorsal raphe, where serotonergic neurons mainly originate from, were investigated by the patch-clamp method in the present study. Tianeptine was shown to inhibit the ion currents induced by the inhibitory neurotransmitters GABA and glycine as well as the inwardly rectifying K + current induced by 5-HT and 8-hydroxy-2 (di- n-propylamino) tetraline hydrobromide (8-OH-DPAT), a 5-HT 1A agonist. Tianeptine, however, exerted no effect on the ion current induced by the excitatory neurotransmitter glutamate. These results indicate that tianeptine has an inhibitory effect on ion currents evoked by GABA, glycine, and inwardly rectifying K + current induced by 5-HT in the dorsal raphe. This action may increase the excitability of serotonergic neurons of the dorsal raphe.