Kley H K, Dehnen H, Krüskemper H L
Arzneimittelforschung. 1979;29(6):885-9.
The effect of the antiserotoninergic agent cyproheptadine (C) on the adrenal system was studied in male rats, the adrenocorticol function of which was assessed by analysis of the urinary excretion of free corticosterone. After a feeding period with 0.5--0.7 mg C/kg body weight/day for several months significant differences in the urinary excretion of free corticosterone were only found when the rats were exposed to systemic stress stimuli as cold (increase from 118.7 +/- 5.3 to 305.5 +/- 5.1 vs. 417.8 +/- 48.6 ng/d in the controls; p less than 0.001) and hunger (no increase of free corticosterone in treated animals as compared to an increase to 446.0 +/- 53.6 ng/d in the controls). In contrast to these findings no effect of C was seen when studying the neurotropic stress stimuli reserpine and ether. The same was true when measuring free corticosterone under basal conditions and after ACTH- or metyrapone stimulation. It is concluded that serotonin plays a major role as hypothalamic neurotransmitter in systemic but not in the studied neurotropic stress stimuli. The site of serotonin action does not comprise adrenal synthesis of steroids and the hypothalamic-pituitary-adrenal feedback system, as is shown by the ACTH- and metyrapone stimulation tests.
在雄性大鼠中研究了抗血清素能药物赛庚啶(C)对肾上腺系统的作用,通过分析游离皮质酮的尿排泄量来评估其肾上腺皮质功能。在以0.5 - 0.7毫克C/千克体重/天的剂量喂食几个月后,仅当大鼠受到全身性应激刺激如寒冷(游离皮质酮尿排泄量从118.7±5.3增加到305.5±5.1,而对照组为417.8±48.6纳克/天;p<0.001)和饥饿(与对照组增加到446.0±53.6纳克/天相比,处理组动物的游离皮质酮无增加)时,游离皮质酮的尿排泄量才出现显著差异。与这些发现相反,在研究神经源性应激刺激利血平和乙醚时未观察到C的作用。在基础条件下以及促肾上腺皮质激素(ACTH)或甲吡酮刺激后测量游离皮质酮时也是如此。结论是,血清素作为下丘脑神经递质在全身性应激刺激中起主要作用,但在所研究的神经源性应激刺激中不起主要作用。促肾上腺皮质激素和甲吡酮刺激试验表明,血清素的作用部位不包括肾上腺类固醇合成以及下丘脑 - 垂体 - 肾上腺反馈系统。