Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland.
Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, 20-093, Lublin, Poland.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Aug;390(8):769-774. doi: 10.1007/s00210-017-1377-0. Epub 2017 Apr 20.
Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and impairment of the central corticotropin-releasing factor (CRF) system are factors in the pathogenesis of depression. Though several antagonists of the CRF receptor were effective in the recognized behavioral tests for antidepressant activity, there is still little information on the potential interactions between CRF receptor inhibitors and conventional antidepressant therapy. The aim of our study was to assess the influence of SN003, a CRF receptor blocker, on the activity of imipramine and fluoxetine in the forced swim test (FST) in rats which presented some signs of depression. The experiments were carried out on female Wistar rats subjected to 14-day subcutaneous corticosterone (CORT) administration (20 mg/kg/day). The antidepressant-like effect was determined by the FST and the CRF levels in the hypothalamus, amygdala, and peripheral blood were measured by a high-sensitivity immunoenzymatic test. SN003 (0.5 mg/kg) potentiated the antidepressant-like effect of imipramine (15 mg/kg) and fluoxetine (7.5 mg/kg). Moreover, the co-administration of the tested agents abolished CORT-induced increase in CRF levels in the examined biological material more profoundly than monotherapy. Our present findings give further evidence that the blockage of CRF action may be useful in the treatment of mood disorders. The concurrent use of well-known antidepressants with CRF receptor antagonists could be beneficial in terms of safety, since it requires lower doses of the applied agents.
下丘脑-垂体-肾上腺轴（HPA）的过度活跃和中枢促肾上腺皮质释放因子（CRF）系统的损伤是抑郁症发病机制的因素。尽管几种 CRF 受体拮抗剂在公认的抗抑郁活性行为测试中有效，但关于 CRF 受体抑制剂与常规抗抑郁治疗之间潜在相互作用的信息仍然很少。我们的研究目的是评估 SN003（一种 CRF 受体阻滞剂）对皮质酮（CORT）（20mg/kg/天）给药 14 天的雌性 Wistar 大鼠中氟西汀和氟西汀在强迫游泳试验（FST）中的活性的影响。具有抑郁迹象的大鼠。通过 FST 确定抗抑郁样作用，通过高灵敏度免疫酶试验测量下丘脑，杏仁核和外周血中的 CRF 水平。SN003（0.5mg/kg）增强了丙咪嗪（15mg/kg）和氟西汀（7.5mg/kg）的抗抑郁样作用。此外，与单药治疗相比，测试药物的联合给药更能消除 CORT 诱导的检查生物材料中 CRF 水平的升高。我们目前的研究结果进一步证明，阻断 CRF 作用可能对抗情绪障碍有用。由于使用的药物剂量较低，因此将已知的抗抑郁药与 CRF 受体拮抗剂同时使用在安全性方面可能是有益的。
