Ascorbic acid treatment, similarly to fluoxetine, reverses depressive-like behavior and brain oxidative damage induced by chronic unpredictable stress

J Psychiatr Res. 2012 Mar;46(3):331-40. doi: 10.1016/j.jpsychires.2011.11.009. Epub 2011 Dec 9.


Reactive oxygen species (ROS) have been shown to play a role in the pathophysiology of depression. Taking into account that experimental chronic unpredictable stress (CUS) induces depressive-like behavior and that ascorbic acid has antidepressant-like effect in animals, the objective of this study was to investigate the influence of ascorbic acid on depressive-like behavior induced by CUS paradigm, serum corticosterone levels and markers of oxidative stress in cerebral cortex and hippocampus of mice. Animals were submitted to CUS procedure during 14 days. From the 8th to the 14th day mice received ascorbic acid (10 mg/kg) or fluoxetine (10 mg/kg, conventional antidepressant, positive control) once a day by oral route. On 15th day behavioral and biochemical parameters were analyzed. CUS exposure caused a depressive-like behavior evidenced by the increased immobility time in the tail suspension test and decreased time in which mice spent grooming in the splash test. Depressive-like behavior induced by CUS was accompanied by a significant increased lipid peroxidation (cerebral cortex and hippocampus), decreased catalase (CAT) (cerebral cortex and hippocampus) and glutathione reductase (GR) (hippocampus) activities and reduced levels of glutathione (cerebral cortex). Repeated ascorbic acid or fluoxetine administration significantly reversed CUS-induced depressive-like behavior and oxidative damage. No alteration was observed in locomotor activity, corticosterone levels and glutathione peroxidase (GPx) activity. These findings indicate a rapid and robust effect of ascorbic acid in reversing behavioral and biochemical alterations induced by CUS in mice, suggesting that this vitamin may be an alternative approach for the management of depressive symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology*
  • Catalase / metabolism
  • Cerebral Cortex / metabolism*
  • Corticosterone / metabolism
  • Depression* / drug therapy
  • Depression* / etiology
  • Depression* / metabolism
  • Disease Models, Animal
  • Fluoxetine / pharmacology*
  • Glutathione / metabolism
  • Glutathione Reductase / metabolism
  • Hippocampus / metabolism*
  • Lipid Peroxidation / drug effects
  • Mice
  • Motor Activity / drug effects
  • Oxidative Stress / drug effects*
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism
  • Treatment Outcome


  • Antidepressive Agents
  • Antioxidants
  • Fluoxetine
  • Catalase
  • Glutathione Reductase
  • Glutathione
  • Ascorbic Acid
  • Corticosterone