Stanić Dušanka, Plećaš-Solarović Bosiljka, Mirković Duško, Jovanović Predrag, Dronjak Slađana, Marković Bojan, Đorđević Tea, Ignjatović Svetlana, Pešić Vesna
Department of Physiology, University of Belgrade, Faculty of Pharmacy, Serbia.
Department of Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Serbia.
Psychoneuroendocrinology. 2017 Jun;80:137-146. doi: 10.1016/j.psyneuen.2017.03.011. Epub 2017 Mar 10.
Chronic stress conditions can lead to considerable and extensible changes in physiological and psychological performances, and in emergence of risk for various somatic diseases. On the other hand, the neuropeptide oxytocin is reported to increase the resistance of the organism to stress and modulate activity of autonomic nervous system. Chronic corticosterone administration is used as a rat model for a state observed in terms of chronic stress exposure, when negative feedback mechanism of hypothalamus-pituitary-adrenal axis activity is disrupted. In our study, we aimed to investigate whether chronic administration of oxytocin (10 IU/400μL/day for 14days, s.c.) influenced adrenal gland morphology and activity in adult male Wistar rats during long-term corticosterone administration via drinking water (100mg/L for 21days). We examined the influence of treatments on the levels of adrenal gland hormones, corticosterone, adrenaline and noradrenaline, as well as their response to an acute stress challenge evoked by 15-min forced swimming. In addition, the expression of two main monoamine transporters, the noradrenaline transporter (NAT) and vesicular monoamine transporter 2 (VMAT2) in adrenal medulla was measured in the rats exposed to acute stress. Our results showed that oxytocin treatment prevented corticosterone-induced decrease in body weight gain, attenuated adrenal gland atrophy by increasing glandular weight, and the area of the zona fasciculate and reticularis. Chronic corticosterone intake blunted the response of all measured hormones to acute stress, whereas concomitant oxytocin treatment reversed adrenaline and noradrenaline response to acute stress. Furthermore, in adrenal medulla, oxytocin produced significant vasodilatation and stimulated expression of both catecholamine transporters detected both on mRNA and protein level. Our data suggest that oxytocin, by reducing atrophy of adrenal gland, and by increasing catecholamine storage capacity, may be beneficial in conditions accompanied with high glucocorticoid levels, such as chronic stress exposure.
慢性应激状态可导致生理和心理表现发生显著且广泛的变化，并引发各种躯体疾病的风险。另一方面，据报道神经肽催产素可增强机体对压力的抵抗力，并调节自主神经系统的活动。慢性给予皮质酮被用作一种大鼠模型，用于模拟在慢性应激暴露时观察到的状态，此时下丘脑 - 垂体 - 肾上腺轴活动的负反馈机制被破坏。在我们的研究中，我们旨在调查慢性给予催产素（10 IU/400μL/天，皮下注射，共14天）是否会影响成年雄性Wistar大鼠在通过饮用水长期给予皮质酮（100mg/L，共21天）期间肾上腺的形态和活性。我们研究了这些处理对肾上腺激素、皮质酮、肾上腺素和去甲肾上腺素水平的影响，以及它们对15分钟强迫游泳引发的急性应激挑战的反应。此外，在暴露于急性应激的大鼠中测量了肾上腺髓质中两种主要单胺转运体，即去甲肾上腺素转运体（NAT）和囊泡单胺转运体2（VMAT2）的表达。我们的结果表明，催产素治疗可防止皮质酮诱导的体重增加减少，通过增加腺体重量、束状带和网状带的面积来减轻肾上腺萎缩。长期摄入皮质酮会减弱所有测量激素对急性应激的反应，而同时给予催产素治疗可逆转肾上腺素和去甲肾上腺素对急性应激的反应。此外，在肾上腺髓质中，催产素可产生显著的血管舒张作用，并在mRNA和蛋白质水平上刺激两种儿茶酚胺转运体的表达。我们的数据表明，催产素通过减少肾上腺萎缩和增加儿茶酚胺储存能力，可能对伴有高糖皮质激素水平的情况有益，如慢性应激暴露。
