Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Apr 3;50:143-50. doi: 10.1016/j.pnpbp.2013.12.012. Epub 2013 Dec 24.
Agmatine has been recently emerged as a novel candidate to assist the conventional pharmacotherapy of depression. The acute restraint stress (ARS) is an unavoidable stress situation that may cause depressive-like behavior in rodents. In this study, we investigated the potential antidepressant-like effect of agmatine (10mg/kg, administered acutely by oral route) in the forced swimming test (FST) in non-stressed mice, as well as its ability to abolish the depressive-like behavior and hippocampal antioxidant imbalance induced by ARS. Agmatine reduced the immobility time in the mouse FST (1-100mg/kg) in non-stressed mice. ARS caused an increase in the immobility time in the FST, indicative of a depressive-like behavior, as well as hippocampal lipid peroxidation, and an increase in the activity of hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, reduced catalase (CAT) activity and increased SOD/CAT ratio, an index of pro-oxidative conditions. Agmatine was effective to abolish the depressive-like behavior induced by ARS and to prevent the ARS-induced lipid peroxidation and changes in SOD, GR and CAT activities and in SOD/CAT activity ratio. Hippocampal levels of reduced glutathione (GSH) were not altered by any experimental condition. In conclusion, the present study shows that agmatine was able to abrogate the ARS-induced depressive-like behavior and the associated redox hippocampal imbalance observed in stressed restraint mice, suggesting that its antidepressant-like effect may be dependent on its ability to maintain the pro-/anti-oxidative homeostasis in the hippocampus.
胍丁胺最近被认为是一种新的候选药物，可以辅助传统的抗抑郁药物治疗。急性束缚应激（ARS）是一种不可避免的应激情况，可能会导致啮齿动物出现类似抑郁的行为。在这项研究中，我们研究了胍丁胺（10mg/kg，经口急性给药）在非应激小鼠强迫游泳试验（FST）中的潜在抗抑郁样作用，以及它消除 ARS 诱导的类似抑郁行为和海马抗氧化失衡的能力。胍丁胺降低了非应激小鼠 FST 中的不动时间（1-100mg/kg）。ARS 导致 FST 中的不动时间增加，表明出现了类似抑郁的行为，以及海马脂质过氧化，以及海马中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）活性增加，过氧化氢酶（CAT）活性降低，SOD/CAT 比值增加，表明氧化条件增加。胍丁胺能有效消除 ARS 诱导的类似抑郁行为，并防止 ARS 诱导的脂质过氧化以及 SOD、GR 和 CAT 活性和 SOD/CAT 活性比值的变化。海马中还原型谷胱甘肽（GSH）的水平不受任何实验条件的影响。总之，本研究表明，胍丁胺能够消除 ARS 诱导的类似抑郁行为和应激束缚小鼠中观察到的相关氧化还原海马失衡，表明其抗抑郁样作用可能依赖于其维持海马中促/抗氧化平衡的能力。
