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This study investigated the antidepressant potential of α-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 α-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 α-tocopheryl phosphate, a water-soluble analogue of α-tocopherol, also reduced the immobility time in the FST (0.1 and 1nmol/site) and in the TST (0.1nmol/site). In addition, the long-term treatment (28 days) with α-tocopherol (10mg/kg, p.o.) significantly reduced the immobility time in the FST. Moreover, a subeffective dose of α-T (10mg/kg, p.o.) potentiated the effect of fluoxetine (10mg/kg, p.o.) in the FST. The long-term treatment with α-T was able to increase the glutathione (GSH) antioxidant defense system, while the acute treatment was not. The long-term treatment with α …