Protective Effects of Ascorbic Acid on Behavior and Oxidative Status of Restraint-Stressed Mice

Abstract

Studies have demonstrated an association between stressful conditions and the onset of clinical depression. Considering the antidepressant-like properties of ascorbic acid in both experimental and clinical approaches, we evaluated the beneficial effect of this vitamin on restraint stress-induced behavioral and neurochemical alterations. Acute restraint stress caused a depressive-like behavior in the forced swimming test, accompanied by increased lipid peroxidation (cerebral cortex and hippocampus); increased superoxide dismutase (cerebral cortex and hippocampus), glutathione reductase (cerebral cortex), and glutathione peroxidase (cerebral cortex and hippocampus) activities; and elevated expression of Bcl-2 (hippocampus). Oral administration of ascorbic acid (1 mg/kg) or fluoxetine (10 mg/kg) 1 h before restraint stress prevented the stress-induced increase on immobility time in the forced swimming test. Moreover, this vitamin reduced lipid peroxidation to control levels and restored the activity of superoxide dismutase, glutathione reductase, and glutathione peroxidase. Ascorbic acid had no effect on the increased level of Bcl-2 induced by stress. Glutathione levels, glycogen synthase kinase-3β phosphorylation, and Bax expression were not altered by stress or ascorbic acid administration. Besides reinforcing the antioxidant potential of ascorbic acid, our results support the notion that oxidative stress plays a role in the pathogenesis and treatment of stress-induced depression.

Acute restraint stress reduces hippocampal oxidative damage and behavior in rats: Effect of S-allyl cysteine

“…In this study, we found that acute restraint stress enhanced lipid peroxidation as an index of oxidative damage. Our results are in accordance with previous findings showing that immobilization stress increases MDA levels in the hippocampus of rats and mice [15,35].…”

Guanosine prevents behavioral alterations in the forced swimming test and hippocampal oxidative damage induced by acute restraint stress

“…at a dose of 5 and 10 mg/kg, respectively, 1 h before the ARS procedure. The doses used were chosen based on previous studies (Bettio et al, 2012;Moretti et al, 2013). Solutions were freshly prepared before administration and administered in a volume of 10 ml/kg.…”

“…ARS protocol was performed as previously described (Freitas et al, 2014;Moretti et al, 2013) 1 h after the treatment with vehicle, guanosine or fluoxetine. The immobilization was applied for a period of 7 h using an individual rodent restraint device made of Plexiglas fenestrate, restraining all physical movement without causing pain.…”

“…In fact, we recently demonstrated that the administration of this nucleoside produces an antidepressant-like effect in the tail suspension test (TST) and in the forced swimming test (FST) similar to the one produced by fluoxetine (Bettio et al, 2012); however, the involvement of this effect with hippocampal anti-/pro-oxidative events has not yet been investigated. Considering this background, the present study investigated the protective effect of guanosine against behavioral alterations in the forced swimming test and hippocampal antioxidant imbalance induced by the acute restraint stress (ARS) protocol (Kumar et al, 2010;Moretti et al, 2013;Freitas et al, 2014).…”

Contributions of animal models to the study of mood disorders

“…56 The administration of classical antidepressants reverses stress-induced biochemical and behavioral changes. 42,[57][58][59][60][61] The animal models of depression induced by different stressful stimuli (chronic mild stress, maternal deprivation, and restraint stress) reproduce alterations in the immune system, 42,62,63 another pathophysiological aspect found in depressive patients. 64 Classical antidepressants can improve mood and response to treatment in these individuals.…”