Behavioural and neurochemical evidence for the decrease of brain extracellular 5-HT by the antidepressant drug tianeptine.

The effects of the novel antidepressant tianeptine on behaviours induced by the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) and the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) were investigated. Tianeptine (10 mg/kg, i.p.) significantly attenuated wet dog shakes (WDS) induced by 5-HTP (75 mg/kg, i.p.; 30 min after carbidopa 25 mg/kg, i.p.). The effect was most marked when 5-HTP and tianeptine were given together. The main metabolite of tianeptine also attenuated WDS. Components of the 5-HT syndrome (i.e. reciprocal forepaw treading, hind limb abduction, flat body posture) induced by 8-OH-DPAT (0.5 mg/kg, s.c.) were unaffected by tianeptine and 5-HTP given both singly or together. However, tianeptine significantly reduced faecal pellet formation but not cage crossings resulting from 8-OH-DPAT administration. These cage crossings but not the associated faecal pellet formation were reduced by 5-HTP. This reduction was prevented by tianeptine. The increase of extracellular 5-HT in the frontal cortex following administration of 5-HTP was opposed and the concurrent increase of extracellular 5-hydroxyindoleacetic acid (5-HIAA) was enhanced by tianeptine. The above behavioural and neurochemical findings indicate that tianeptine opposes the increase of 5-HT at receptor sites due to 5-HTP administration.