Abstract：
:The effects of acute and chronic administration of tianeptine, a novel antidepressant agent, on the hypothalamo-pituitary-adrenal axis were studied in the adult male rat. A single injection of tianeptine did not alter the activity of the hypothalamo-pituitary-adrenal axis. In contrast, chronic administration of tianeptine (10 mg/kg twice a day for 15 days) induced a significant decrease in the concentration of corticotropin-releasing factor (CRF) in the hypothalamus and adrenocorticotropin (ACTH) in the anterior lobe of the pituitary. Chronic tianeptine treatment did not modify CRF levels in the cerebral cortex and hippocampus, and did not alter alpha-melanocyte-stimulating hormone and beta-endorphin levels in the neurointermediate lobe of the pituitary. Using the in situ hybridization technique, we observed that chronic administration of tianeptine did not modify CRF mRNA levels in the paraventricular nucleus of the hypothalamus. The effect of chronic tianeptine treatment on the neuroendocrine response to stress was also investigated. Tube restraint stress for 30 min induced a significant depletion of hypothalamic CRF and a substantial increase of plasma ACTH and corticosterone. Tianeptine abolished the stress-induced reduction of hypothalamic CRF concentration and markedly reduced the stress-induced increase in plasma ACTH and corticosterone levels. Taken together, these results suggest that tianeptine acts primarily at the level of the hypothalamus: (1) in unstressed rats, tianeptine reduces hypothalamic CRF and pituitary ACTH contents; (2) in stressed animals, tianeptine attenuates the activation of the hypothalamo-pituitary-adrenal axis.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Delbende C,Tranchand Bunel D,Tarozzo G,Grino M,Oliver C,Mocaër E,Vaudry Hdoi
10.1016/0014-2999(94)90406-5subject
Has Abstractpub_date
1994-01-14 00:00:00pages
245-51issue
2-3eissn
0014-2999issn
1879-0712pii
0014-2999(94)90406-5journal_volume
251pub_type
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