Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-900 Florianópolis, SC, Brazil.
Behav Brain Res. 2010 Jun 19;209(2):249-59. doi: 10.1016/j.bbr.2010.02.002. Epub 2010 Feb 6.
This study investigated the antidepressant potential of alpha-tocopherol, the most active and abundant form of vitamin E, in the forced swim test (FST) and tail suspension test (TST). The acute oral treatment with alpha-tocopherol at the doses of 30 and 100mg/kg reduced the immobility time in the FST and in the TST. A single i.c.v. administration of alpha-tocopheryl phosphate, a water-soluble analogue of alpha-tocopherol, also reduced the immobility time in the FST (0.1 and 1 nmol/site) and in the TST (0.1 nmol/site). In addition, the long-term treatment (28 days) with alpha-tocopherol (10mg/kg, p.o.) significantly reduced the immobility time in the FST. Moreover, a subeffective dose of alpha-T (10mg/kg, p.o.) potentiated the effect of fluoxetine (10mg/kg, p.o.) in the FST. The long-term treatment with alpha-T was able to increase the glutathione (GSH) antioxidant defense system, while the acute treatment was not. The long-term treatment with alpha-tocopherol (10mg/kg) increased the GSH levels in the hippocampus and in the prefrontal cortex and increased the glutathione peroxidase and glutathione reductase activity in the hippocampus (10mg/kg) and in the prefrontal cortex (10-100mg/kg). The long-term treatment with fluoxetine (10mg/kg, p.o.), a positive control, was also able to increase the GSH levels in the hippocampus, but failed to alter the activity of both enzymes. Besides the specific antidepressant-like effect, long-term, but not the acute treatment with alpha-T, especially in the doses that produced an antidepressant-like effect (10mg/kg), improved the antioxidant defenses in the mouse hippocampus and prefrontal cortex, two structures closely implicated in the pathophysiology of depression.
本研究探讨了 α-生育酚（维生素 E 最活跃和最丰富的形式）在强迫游泳试验（FST）和悬尾试验（TST）中的抗抑郁作用。急性口服 α-生育酚 30 和 100mg/kg 剂量可减少 FST 和 TST 中的不动时间。单次侧脑室注射水溶性 α-生育酚磷酸盐类似物 α-生育酚磷酸酯（0.1 和 1nmol/部位）也可减少 FST（0.1nmol/部位）和 TST（0.1nmol/部位）中的不动时间。此外，长期（28 天）口服 α-生育酚（10mg/kg）可显著减少 FST 中的不动时间。此外，亚有效剂量的 α-T（10mg/kg）增强了氟西汀（10mg/kg）在 FST 中的作用。长期 α-T 治疗能够增加谷胱甘肽（GSH）抗氧化防御系统，而急性治疗则不能。长期（10mg/kg）治疗可增加海马和前额叶皮层中的 GSH 水平，并增加海马（10mg/kg）和前额叶皮层（10-100mg/kg）中的谷胱甘肽过氧化物酶和谷胱甘肽还原酶活性。阳性对照氟西汀（10mg/kg，po）长期治疗也能增加海马中的 GSH 水平，但不能改变两种酶的活性。除了特定的抗抑郁样作用外，长期（而非急性）治疗 α-T，特别是在产生抗抑郁样作用的剂量（10mg/kg）时，可改善小鼠海马和前额叶皮层的抗氧化防御能力，这两个结构与抑郁的病理生理学密切相关。
