Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Islamic Republic of Iran.
J Basic Clin Physiol Pharmacol. 2020 Oct 5;32(2):25-31. doi: 10.1515/jbcpp-2020-0021.
Previous studies have suggested antidepressant properties for modafinil; however, the underlying mechanisms mediating the antidepressant effect of modafinil have not been well recognized in clinical and animal studies. Nitric oxide (NO) is involved in the pathophysiology of depression. We attempted to investigate the possible role of NO in the antidepressant-like effect of modafinil in mouse forced swimming test (FST) and tail suspension test (TST).
The antidepressant-like effect of modafinil (25, 50 and 75 mg/kg), alone and in combination with l-arginine, l-arg, (100 mg/kg) and N-l-arginine methyl ester, l-NAME (5 mg/kg), was evaluated using FST and TST. Following behavioral tests, the hippocampi were dissected out to measure nitrite levels.
Findings suggested that administration of modafinil at doses of 50 and 75 mg/kg significantly reduced immobility time in the FST and TST. Furthermore, administration of l-arg and l-NAME increased and decreased, respectively, the immobility time in the FST and TST. We showed that co-administration of a sub-effective dose of modafinil (25 mg/kg) plus l-NAME potentiated the antidepressant-like effect of the sub-effective dose of modafinil. In addition, co-treatment of an effective dose of modafinil (75 mg/kg) with l-arg attenuated the antidepressant-like effect of the effective dose of modafinil. We showed that the antidepressant-like effect of modafinil is associated with decreased nitrite levels in the hippocampus.
Our findings for the first time support that the modulation of NO, partially at least, is involved in the antidepressant-like effect of modafinil in mouse FST and TST.
先前的研究表明莫达非尼具有抗抑郁作用；然而，在临床和动物研究中，莫达非尼抗抑郁作用的潜在机制尚未得到很好的认识。一氧化氮（NO）参与了抑郁症的病理生理学过程。我们试图研究 NO 在莫达非尼对小鼠强迫游泳试验（FST）和悬尾试验（TST）的抗抑郁样作用中的可能作用。
使用 FST 和 TST 评估莫达非尼（25、50 和 75mg/kg）单独以及与 l-精氨酸（100mg/kg）和 N- l-精氨酸甲酯（l-NAME，5mg/kg）联合应用的抗抑郁样作用。行为测试后，取出海马测量亚硝酸盐水平。
研究结果表明，50 和 75mg/kg 剂量的莫达非尼给药显著减少了 FST 和 TST 中的不动时间。此外，l-arg 和 l-NAME 的给药分别增加和减少了 FST 和 TST 中的不动时间。我们表明，亚有效剂量的莫达非尼（25mg/kg）与 l-NAME 联合给药增强了亚有效剂量的莫达非尼的抗抑郁样作用。此外，有效剂量的莫达非尼（75mg/kg）与 l-arg 联合治疗减弱了有效剂量的莫达非尼的抗抑郁样作用。我们表明，莫达非尼的抗抑郁样作用与海马中亚硝酸盐水平的降低有关。
我们的研究结果首次支持，NO 的调节至少部分参与了莫达非尼在小鼠 FST 和 TST 中的抗抑郁样作用。
