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

• Published in: Behavioural brain research Vol. 209; no. 2; pp. 249 - 259
• Main Authors: Lobato, Kelly R., Cardoso, Chandra C., Binfaré, Ricardo W., Budni, Josiane, Wagner, Cristiane L.R., Brocardo, Patrícia S., de Souza, Luiz Felipe, Brocardo, Caroline, Flesch, Samira, Freitas, Andiara E., Dafré, Alcir L., Rodrigues, Ana Lúcia S.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 19-06-2010; Elsevier
• Subjects: Adult and adolescent clinical studies; alpha-Tocopherol - analogs & derivatives; alpha-Tocopherol - pharmacology; Analysis of Variance; Animals; Antidepressive Agents - pharmacology; Behavioral psychophysiology; Biological and medical sciences; Depression; Depressive Disorder - drug therapy; Disease Models, Animal; Exploratory Behavior - drug effects; Female; Fluoxetine - pharmacology; Forced swimming test; Fundamental and applied biological sciences. Psychology; Glutathione; Glutathione - analysis; Hindlimb Suspension; Hippocampus - chemistry; Hippocampus - drug effects; Immobility Response, Tonic - drug effects; Medical sciences; Mice; Mood disorders; Motor Activity - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Prefrontal Cortex - chemistry; Prefrontal Cortex - drug effects; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychopharmacology; Swimming; Tail suspension test; Time Factors; α-Tocopherol; α-Tocopheryl phosphate; NADPH; Forced swimming test; GSSG; α-Tocopheryl phosphate; DTNB; FST; α-Tocopherol; GR; GPx; Tail suspension test; p.o; TST; ANOVA; α-T; α-TP; GSH; Glutathione; Mood disorder; Phosphates; Animal model; Psychotropic; Vitamin; Prediction; Depression; Suspension; Antioxidant; Stress; Micronutrient; Tail; Antidepressant agent
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2010.02.002

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 100
mg/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 1
nmol/site) and in the TST (0.1
nmol/site). In addition, the long-term treatment (28 days) with α-tocopherol (10
mg/kg, p.o.) significantly reduced the immobility time in the FST. Moreover, a subeffective dose of α-T (10
mg/kg, p.o.) potentiated the effect of fluoxetine (10
mg/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-tocopherol (10
mg/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 (10
mg/kg) and in the prefrontal cortex (10–100
mg/kg). The long-term treatment with fluoxetine (10
mg/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 α-T, especially in the doses that produced an antidepressant-like effect (10
mg/kg), improved the antioxidant defenses in the mouse hippocampus and prefrontal cortex, two structures closely implicated in the pathophysiology of depression.