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  • Title: Tianeptine stimulates uptake of 5-hydroxytryptamine in vivo in the rat brain.
    Author: Fattaccini CM, Bolaños-Jimenez F, Gozlan H, Hamon M.
    Journal: Neuropharmacology; 1990 Jan; 29(1):1-8. PubMed ID: 1689469.
    Abstract:
    The neurochemical effects of the atypical tricyclic antidepressant, tianeptine, were further assessed on central serotoninergic and dopaminergic systems in the rat. Acute treatment with tianeptine (10 mg/kg i.p.) significantly enhanced the levels of metabolites of 5-HT and DA, 5-hydroxyindole acetic acid and dihydroxyphenylacetic acid respectively, in the brain stem, striatum and cerebral cortex. These effects could be prevented by the administration of drugs acting selectively (or preferentially) on serotoninergic systems such as d,l-fenfluramine and 4-methyl-alpha-ethyl-metatyramine (H75/12), suggesting that the increased metabolism of DA was secondary to a modification of serotoninergic systems in tianeptine-treated rats. In contrast to that found with inhibitors of the uptake of 5-HT, treatment with tianeptine markedly enhanced depletion of 5-HT due to administration of H75/12. However, depletion of DA induced by H75/12, was not altered by tianeptine. In vitro measurement of the uptake of [3H]5-HT also confirmed that tianeptine exerted opposite effects to those of classical tricyclic antidepressants, since the in vivo administration of tianeptine (2 x 10 mg/kg i.p.) induced a significant increase in the uptake of [3H]5-HT in cortical synaptosomes. The fact that both inhibitors of the uptake of 5-HT and tianeptine which, in contrast, enhanced the in vivo uptake of 5-HT, are potent antidepressants, challenges the current hypothesis on the central mechanisms of action of these drugs.
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