Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Department of Biochemistry and Pharmacology, Faculty of Pharmacy, Federal University of Piauí, Teresina, Piauí, Brazil.
Pharmacol Biochem Behav. 2019 May;180:44-51. doi: 10.1016/j.pbb.2019.03.005. Epub 2019 Mar 20.
Mental disorders have a multifactorial etiology and stress presents as one of the causal factors. In depression, it is suggested that high cortisol concentration contributes directly to the pathology of this disease. Based on that, the study aims to evaluate the potential antidepressant effect of Riparin IV (Rip IV) in mice submitted to chronic stress model by repeated corticosterone administration. Female Swiss mice were selected into four groups: control (Ctrl), corticosterone (Cort), Riparin IV (Cort + Rip IV) and fluvoxamine (Cort + Flu). Three groups were administrated subcutaneously (SC) with corticosterone (20 mg/kg) during twenty-one days, while the control group received only vehicle. After the fourteenth day, groups were administrated tested drugs: Riparin IV, fluvoxamine or distilled water, by gavage, 1 h after subcutaneous injections. After the final treatment, animals were exposed to behavioral models such as forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated plus maze (EPM) and sucrose preference test (SPT). The hippocampus was also removed for the determination of BDNF levels. Corticosterone treatment altered all parameters in behavioral tests, leading to a depressive- and anxious-like behavior. Riparin IV and fluvoxamine exhibit antidepressant effect in FST, TST and SPT. In EPM and OFT, treatment displayed anxiolytic effect without alteration of locomotor activity. Corticosterone administration decreased BDNF levels and Riparin IV could reestablish them, indicating that its antidepressant effect may be related to ability to ameliorate hippocampal neurogenesis. These findings suggest that Riparin IV improves the depressive and anxious symptoms after chronic stress and could be a new alternative treatment for patients with depression.
精神障碍的病因复杂，压力是其中一个致病因素。在抑郁症中，高皮质醇浓度被认为直接导致了这种疾病的发生。基于这一点，本研究旨在通过重复给予皮质酮来评估 Riparin IV（Rip IV）对慢性应激模型小鼠的潜在抗抑郁作用。选择雌性瑞士小鼠分为四组：对照组（Ctrl）、皮质酮组（Cort）、Riparin IV 组（Cort+Rip IV）和氟伏沙明组（Cort+Flu）。三组小鼠接受二十一天的皮下注射皮质酮（20mg/kg），对照组仅接受载体处理。在第十四天，各组给予 Riparin IV、氟伏沙明或蒸馏水灌胃，在皮下注射后 1 小时进行。最后一次处理后，动物暴露于强迫游泳试验（FST）、悬尾试验（TST）、旷场试验（OFT）、高架十字迷宫试验（EPM）和蔗糖偏好试验（SPT）等行为模型中。还取出海马以测定 BDNF 水平。皮质酮处理改变了行为测试中的所有参数，导致抑郁样和焦虑样行为。Riparin IV 和氟伏沙明在 FST、TST 和 SPT 中表现出抗抑郁作用。在 EPM 和 OFT 中，治疗显示出抗焦虑作用，而不改变运动活性。皮质酮给药降低了 BDNF 水平，而 Riparin IV 可以恢复它们，这表明其抗抑郁作用可能与改善海马神经发生的能力有关。这些发现表明，Riparin IV 可改善慢性应激后抑郁和焦虑症状，可能是治疗抑郁症患者的一种新的替代治疗方法。
