[Electrophysiological study of tianeptine, a new enhancer of serotonin uptake with antidepressant activity]

Tianeptine is a clinically effective antidepressant, not chemically related to classical tricyclic compounds. Its mechanism of action preferentially involves central serotoninergic transmissions, by increasing uptake after acute and chronic administration in rat brain and platelets and in human platelets. We studied the effects of tianeptine on three currently used electrophysiological methods: Ro4-1284 induced PGO waves in the cat, neocortical EEG activity in the acute rat preparation and sleep-wakefulness modifications in chronically implanted rats. Density of Ro4-1284 induced PGO waves was reduced by tianeptine, the minimal effective dose being 2 mg.kg-1i.v. (ED50 = 2.9 mg.kg-1i.v.). In acute rat preparation, the low voltage fast waves basal EEG pattern was not modified by tianeptine in a dose range of 1.25 to 20 mg.kg-1i.p. Higher dosage (25 mg.kg-1i.p.) induced high amplitude episodes with few or no delta waves. Low doses which did not apparently modify acute EEG have been tested on sleep-wakefulness cycle in implanted rats. Tianeptine, after single administration, did not modify sleep states up to 2.5 mg.kg-1i.p. An increased wakefulness was observed during the first hour after 5-10 mg.kg-1i.p., afterwards sleep states returned to control values up to 12 h. A subsequent 12 h recording performed 24 h after treatment did not show any change compared to pretreatment baseline. After sub-chronic administration (2.5 mg.kg-1i.p./day, 9 days) no change was observed in sleepwake pattern during or after cessation of treatment. Tianeptine EEG profile is radically different from those usually induced by classical tricyclic antidepressants.