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The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation.

McEwen BS, Chattarji S, Diamond DM, Jay TM, Reagan LP, Svenningsson P, Fuchs E - Mol. Psychiatry (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA. mcewen@mail.rockefeller.edu

ABSTRACT
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.

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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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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).

Mentions: In the amygdala Reagan and coworkers (57) have examined the stress modulation of extracellular glutamate levels in the basolateral nucleus and the central nucleus of the amygdala by in vivo microdialysis. Acute stress increased extracellular glutamate levels in the basolateral and central nuclei of the amygdala and tianeptine normalises synaptic concentrations of glutamate in the rat basolateral nucleus of the amygdala (Figure 3). Tianeptine also modulates the stress-induced changes observed in the expression of glial glutamate transporters that represent the sole mechanism through which the activity of glutamate is terminated in excitatory synapses (111).


The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation.

McEwen BS, Chattarji S, Diamond DM, Jay TM, Reagan LP, Svenningsson P, Fuchs E - Mol. Psychiatry (2009)

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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Related In: Results  -  Collection

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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).
Mentions: In the amygdala Reagan and coworkers (57) have examined the stress modulation of extracellular glutamate levels in the basolateral nucleus and the central nucleus of the amygdala by in vivo microdialysis. Acute stress increased extracellular glutamate levels in the basolateral and central nuclei of the amygdala and tianeptine normalises synaptic concentrations of glutamate in the rat basolateral nucleus of the amygdala (Figure 3). Tianeptine also modulates the stress-induced changes observed in the expression of glial glutamate transporters that represent the sole mechanism through which the activity of glutamate is terminated in excitatory synapses (111).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA. mcewen@mail.rockefeller.edu

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus