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Effect of the antidepressant tianeptine on the activity of the hypothalamo-pituitary-adrenal axis

Published online by Cambridge University Press:  16 April 2020

C Delbende ,
E Mocaër ,
M Rettori ,
A Kamoun  and
H Vaudry
C Delbende*
Affiliation:
European Institute for Peptide Research, Laboratory of Molecular Endocrinology, CNRS URA 650, UA INSERM, University of Rouen, 76134Mont-Saint-Aignan
E Mocaër
Affiliation:
Institut de Recherches Internationales Servier, 6 place des Pléiades, 92415Courbevoie Cedex, France
M Rettori
Affiliation:
Institut de Recherches Internationales Servier, 6 place des Pléiades, 92415Courbevoie Cedex, France
A Kamoun
Affiliation:
Institut de Recherches Internationales Servier, 6 place des Pléiades, 92415Courbevoie Cedex, France
H Vaudry*
Affiliation:
European Institute for Peptide Research, Laboratory of Molecular Endocrinology, CNRS URA 650, UA INSERM, University of Rouen, 76134Mont-Saint-Aignan
*
*Present address: Laboratoire de Biologie Animate, Université des Sciences et Technologies de Lille I, 59655 Villeneuve d'Ascq, France.
** Correspondence and reprints.
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Summary

The effect of the antidepressant agent, tianeptine, on the hypothalamo-pituitary-adrenal (HPA) axis was studied in adult male rats under basal and stressed conditions. Chronic treatment with tianeptine (10 mg/kg; 2 weeks; twice a day) induced a significant decrease of hypothalamic CRF (–12%) and pituitary ACTH concentrations (–21%), suggesting that tianeptine reduces the activity of hypothalamic CRF neurons and pituitary corticotrophs. The possible effect of tianeptine in the neuroendocrine response to stress was thus investigated. Rats were submitted to restraint stress for 30 min; under these conditions ACTH and corticosterone levels were considerably increased. A single injection of tianeptine was found to significantly reduce stress-evoked elevations of plasma ACTH and corticosterone. Time-course experiments, consisting of administering tianeptine 1–3 h before immobilization stress, revealed that the maximum inhibitory effect of tianeptine occurs about 2 h after injection of the antidepressant. Administration of various doses of tianeptine (from 2.5 to 20 mg/kg) showed that the effect of the drug was dose-dependent; the maximum effective dose being 10 mg/kg. Taken together, these data indicate that tianeptine may exert original ‘anti-stress’ activity.

Keywords

CRF (corticotropin-releasing factor)ACTH (adrenocorticotropic hormone)corticosteroneimmobilization stress5-HT (5-hydroxytryptamine, serotonin)hypothalamo-pituitary-adrenal axisantidepressanttianeptine
Type
Research Article
Information
European Psychiatry , Volume 8 , Issue S2: Neuroendocrinological aspects of depression 28 June 1992, Nice, France , 1993 , pp. 49s - 54s
Copyright
Copyright © Elsevier, Paris 1993

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