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.
Lobato
Kelly R
KR
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-900 Florianópolis, SC, Brazil.
Cardoso
Chandra C
CC
Binfaré
Ricardo W
RW
Budni
Josiane
J
Wagner
Cristiane L R
CL
Brocardo
Patrícia S
PS
de Souza
Luiz Felipe
LF
Brocardo
Caroline
C
Flesch
Samira
S
Freitas
Andiara E
AE
Dafré
Alcir L
AL
Rodrigues
Ana Lúcia S
AL
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