alpha-Tocopherol administration produces an antidepressant-like effect in predictive animal models of depression.

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.

Evidence for the involvement of the monoaminergic system in the antidepressant-like effect of magnesium.

Literature data has shown that acute administration of magnesium reduces immobility time in the mouse forced swimming test (FST), which suggests potential antidepressant activity in humans. However, its mechanism of action is not completely understood. Thus, this study is aimed at investigating the antidepressant-like action of magnesium and the possible involvement of the monoaminergic system in its effect in the FST. The immobility time in the FST was significantly reduced by magnesium chloride administration (30-100 mg/kg, i.p.) without accompanying changes in ambulation when assessed in an open-field test. The pre-treatment of mice with NAN-190 (0.5 mg/kg, i.p. a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), ketanserin (5 mg/kg, a preferential 5-HT(2A) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), haloperidol (0.2 mg/kg, i.p., a non selective dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist) 30 min before the administration of magnesium chloride (30 mg/kg, i.p.) significantly prevented its anti-immobility effect in the FST. Moreover, the administration of sub-effective doses of fluoxetine (10 mg/kg, i.p., serotonin reuptake inhibitor), imipramine (5 mg/kg, i.p., a mixed serotonergic noradrenergic reuptake inhibitor), bupropion (1 mg/kg, i.p., dopamine reuptake inhibitor) was able to potentiate the action of sub-effective doses of magnesium chloride. In conclusion, the present study provides evidence indicating that the antidepressant-like effect of magnesium in the FST is dependent on its interaction with the serotonergic (5-HT(1A) and 5-HT(2A/2C) receptors), noradrenergic (alpha(1)- and alpha(2)- receptors) and dopaminergic (dopamine D(1) and D(2) receptors) systems.