Protective effects of ascorbic acid on behavior and oxidative status of restraint-stressed mice

J Mol Neurosci. 2013 Jan;49(1):68-79. doi: 10.1007/s12031-012-9892-4. Epub 2012 Oct 3.


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.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use*
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / metabolism
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / etiology
  • Female
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / genetics
  • Glutathione Reductase / metabolism
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Hippocampus / enzymology
  • Hippocampus / metabolism
  • Lipid Metabolism / drug effects
  • Mice
  • Motor Activity / drug effects
  • Oxidation-Reduction / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stress, Psychological / complications*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Swimming
  • Transcription, Genetic / drug effects
  • Vitamins / pharmacology
  • Vitamins / therapeutic use*
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Antioxidants
  • Bax protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • Vitamins
  • bcl-2-Associated X Protein
  • Bcl2 protein, mouse
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3
  • Ascorbic Acid