Department of Medical Genetics, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran.
Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
Biomed Pharmacother. 2019 Jan;109:589-594. doi: 10.1016/j.biopha.2018.10.033. Epub 2018 Nov 3.
It is now well-established that orexins (OXs) and their receptors are involved in the pathophysiology of depression. Considering the evidence indicating the importance of nitric oxide (NO) system in the mood modulation, this study investigated the effect of intraperitoneal (i.p.) administration of orexin 1 (OX1) receptor antagonist -SB334867- alone or in combination with NO agents on depression using the forced swimming test (FST), tail suspension test (TST) and the number of crossings in open-field test (OFT) in mice. Our results indicated that administration of SB334867 at the dose of 0.5 mg/kg decreased the immobility time in the FST without effect on locomotor activity, suggesting an antidepressant-like effect of SB334867. Moreover, l-Arginine (a NO precursor; 750 mg/kg) or L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor, 10 mg/kg) administration by itself decreased the immobility time in the FST. Interestingly, co-administration of a sub-threshold dose of L-NAME, but not l-Arginine, in combination with an ineffective dose of SB334867 produced an antidepressant-like effect in the FST and TST. It should be noted, none of the drugs elicited significant effects on the locomotor activity in the OFT. Altogether, the present data propose that a combination of the sub-effective dose of OX and NO antagonists can be evaluated as an option for the clinical treatment of depression in humans.
现已明确，食欲素（OXs）及其受体参与了抑郁症的病理生理学。鉴于表明一氧化氮（NO）系统在情绪调节中的重要性的证据，本研究使用强迫游泳试验（FST）、悬尾试验（TST）和旷场试验（OFT）中的穿越次数，研究了腹腔内（i.p.）给予食欲素 1（OX1）受体拮抗剂-SB334867-单独或与 NO 剂联合给药对抑郁的影响。在小鼠中。我们的结果表明，在 0.5mg/kg 的剂量下给予 SB334867 可减少 FST 中的不动时间，而对运动活性没有影响，表明 SB334867 具有抗抑郁样作用。此外，L-精氨酸（NO 前体；750mg/kg）或 L-NAME（一种非选择性一氧化氮合酶（NOS）抑制剂，10mg/kg）单独给药本身可减少 FST 中的不动时间。有趣的是，亚阈值剂量的 L-NAME 与无效剂量的 SB334867 联合给药会产生 FST 和 TST 中的抗抑郁样作用。应该注意的是，这些药物都没有在 OFT 中引起运动活性的显著变化。总而言之，目前的数据表明，联合使用亚有效剂量的 OX 和 NO 拮抗剂可以作为治疗人类抑郁症的临床选择进行评估。
