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.
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-900 Florianópolis, SC, Brazil.
Kelly R
KR
Lobato
Chandra C
CC
Cardoso
Ricardo W
RW
Binfaré
Josiane
J
Budni
Cristiane L R
CL
Wagner
Patrícia S
PS
Brocardo
Luiz Felipe
LF
de Souza
Caroline
C
Brocardo
Samira
S
Flesch
Andiara E
AE
Freitas
Alcir L
AL
Dafré
Ana Lúcia S
AL
Rodrigues
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D046353:Immobility Response, Tonic / Q000187:drug effects*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000737:chemistry / Q000187:drug effects; D013550:Swimming; D013997:Time Factors; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000928:Antidepressive Agents; D005473:Fluoxetine; D005978:Glutathione; D024502:alpha-Tocopherol