Delbende C, Tranchand Bunel D, Tarozzo G, Grino M, Oliver C, Mocaër E, Vaudry H
European Institute for Peptide Research, CNRS URA 650, UA INSERM, University of Rouen, Mont-Saint-Aignan, France.
Eur J Pharmacol. 1994 Jan 14;251(2-3):245-51. doi: 10.1016/0014-2999(94)90406-5.
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.
在成年雄性大鼠中研究了新型抗抑郁药噻奈普汀急性和慢性给药对下丘脑 - 垂体 - 肾上腺轴的影响。单次注射噻奈普汀未改变下丘脑 - 垂体 - 肾上腺轴的活性。相比之下，慢性给予噻奈普汀（每天两次，每次10mg/kg，共15天）导致下丘脑促肾上腺皮质激素释放因子（CRF）浓度和垂体前叶促肾上腺皮质激素（ACTH）显著降低。慢性噻奈普汀治疗未改变大脑皮层和海马中的CRF水平，也未改变垂体神经中间叶中的α - 黑素细胞刺激素和β - 内啡肽水平。使用原位杂交技术，我们观察到慢性给予噻奈普汀未改变下丘脑室旁核中的CRF mRNA水平。还研究了慢性噻奈普汀治疗对应激神经内分泌反应的影响。30分钟的束缚应激导致下丘脑CRF显著减少以及血浆ACTH和皮质酮大幅增加。噻奈普汀消除了应激诱导的下丘脑CRF浓度降低，并显著降低了应激诱导的血浆ACTH和皮质酮水平升高。综上所述，这些结果表明噻奈普汀主要作用于下丘脑水平：（1）在无应激的大鼠中，噻奈普汀降低下丘脑CRF和垂体ACTH含量；（2）在应激动物中，噻奈普汀减弱下丘脑 - 垂体 - 肾上腺轴的激活。
