In vitro activity: Tianeptine treatment prevents the CMS-induced increase in corticotropin-releasing factor (CRF) mRNA levels in the dBNST, and reduces corticotropin-releasing factor (CRF) mRNA levels in dBNST in non-stressed rats. Tianeptine treatment significantly decreases CRF mRNA levels in the ventral BNST and CeA of non-stressed controls as well as CMS-exposed rats. Tianeptine blocks the stress-induced suppression of PB potentiation in CA1 without affecting the stress-induced enhancement of LTP in basolateral nucleus (BLA) of the amygdala in anesthetized rats. Tianeptine administered under non-stress conditions enhances PB potentiation in the hippocampus and LTP in the amygdala in anesthetized rats. Tianeptine attenuates the behavioral signs of sickness behavior induced by peripheral, but not central, LPS or IL-1beta in the rats. Tianeptine results in a normalized scaling of the amplitude ratio of NMDA receptor to AMPA/kainate receptor-mediated currents and prevents the stress-induced attenuation of NMDA-EPSCs deactivation in rats. Tianeptine treatment significantly reduces apoptosis in the temporal cortex and dentate gyrus, both in control and stressed animals, but has no effect in the Ammons Horn. Tianeptine (2.5 mg/kg, i.v.) increases the extracellular dopamine only in the nucleus accumbens. Tianeptine significantly raises the extracellular concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in both nucleus accumbens and striatum.