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. 2010 Mar;15(3):237-49.
doi: 10.1038/mp.2009.80. Epub 2009 Aug 25.

The Neurobiological Properties of Tianeptine (Stablon): From Monoamine Hypothesis to Glutamatergic Modulation

Free PMC article

The Neurobiological Properties of Tianeptine (Stablon): From Monoamine Hypothesis to Glutamatergic Modulation

B S McEwen et al. Mol Psychiatry. .
Free PMC article


Tianeptine is a clinically used antidepressant that has drawn much attention, because this compound challenges traditional monoaminergic hypotheses of depression. It is now acknowledged that the antidepressant actions of tianeptine, together with its remarkable clinical tolerance, can be attributed to its particular neurobiological properties. The involvement of glutamate in the mechanism of action of the antidepressant tianeptine is consistent with a well-developed preclinical literature demonstrating the key function of glutamate in the mechanism of altered neuroplasticity that underlies the symptoms of depression. This article reviews the latest evidence on tianeptine's mechanism of action with a focus on the glutamatergic system, which could provide a key pathway for its antidepressant action. Converging lines of evidences demonstrate actions of tianeptine on the glutamatergic system, and therefore offer new insights into how tianeptine may be useful in the treatment of depressive disorders.


Figure 1
Figure 1. Tianeptine regulates neuronal plasticity in the amygdala
Rat dendritic arborization in the basolateral amygdale (BLA) increases after repeated chronic (10 days) immobilization stress. This stress-induced enhancement in dendritic arborization in BLA neurons is prevented by daily application of tianeptine (10mg/kg, i.p.). There is a significant decrease in the total dendritic length of BLA neurons from stressed animals treated by tianeptine (1770 ± 107μm) when compared to stressed animals the vehicle (2213 ± 59μm, p<0.001). A similar effect is seen in the number of branch points (15.6±0.9 number of branch points in stressed animals receiving vehicle versus 12 ± 1 in stressed animals treated by tianeptine).CIS:chronic immobilization stress ; Veh: vehicle. ***: p<0.001. Data are means ± SEM.
Figure 2
Figure 2. Regulation of AMPA receptor phosphorylation by tianeptine
The amounts of (A and C) phospho-Ser831-GluR1 and (B and D) phospho-Ser845-GluR1 were measured in the frontal cortex and in the CA3 and CA1 regions of hippocampus from animals treated (A and B) acutely or (C and D) chronically with saline (white bars) or tianeptine (black bars). Chronic treatment with tianeptine increased phospho-Ser831-GluR1 in both the frontal cortex and the CA3 region of hippocampus and phospho-Ser845-GluR1 in the CA3 region of hippocampus. Data are means ± SEM for n = 8–16 animals. Anova followed by Newman Keul’s test for pairwaise comparisons; *P < 0.05 compared with saline-treated animals. From Svenningsson et al. (2007).
Figure 3
Figure 3. Tianeptine, but not fluoxetine, attenuated stress-induced glutamate release in amygdala
(A) Administration of tianeptine 30 min prior to the acute restraint stress session inhibited the stress-induced increases in extracellular glutamate levels in the basolateral amygdala (BLA); conversely, fluoxetine treatment increased basal BLA glutamate efflux and did not modulate the increases elicited by stress. (B) Tianeptine did not inhibit stress-mediated increases in extracellular glutamate levels in the central amygdala (CeA). Similar to observations in the BLA, fluoxetine administration increased glutamate efflux in the CeA in the prestress period, increases that were potentiated during stress. Data (means ± SEM) are based upon six rats per amygdalar nucleus for each drug. *P < 0.05 vs. baseline; $P < 0.05 vs. saline; #P < 0.05 vs. tianeptine. From Reznikov et al. (2007).

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