Chronic social isolation decreases glutamate and glutamine levels and induces oxidative stress in the rat hippocampus

Behav Brain Res. 2015 Apr 1:282:201-8. doi: 10.1016/j.bbr.2015.01.005. Epub 2015 Jan 12.


Social isolation (SI) rearing of rodents is a developmental manipulation, which is commonly compared with the psychological stressors in humans as it produces several behavioral outcomes similar to those observed in humans with early life stress. To explain the SI-induced behavioral outcomes, animal studies have been performed to examine the dopaminergic and glutamatergic systems in the brain. In this study, we measured possible changes in levels of glutamate and glutamine of SI-rats using proton magnetic resonance spectroscopy. We also assessed the oxidative stress parameters in certain brain regions to see if glutamate and/or glutamine changes, if any, are associated with oxidative stress. SI rearing for 8 weeks decreased the activities of antioxidant enzymes catalase, glutathione peroxidase, superoxide dismutase, and the total antioxidant capacity, but increased levels of hydrogen peroxide, in certain brain regions, of which prefrontal cortex and hippocampus were most vulnerable. It also decreased levels of glutamate, glutamine, N-acetyl-l-aspartate (NAA), and phosphocreatine in the dorsal hippocampus, but not in the cerebral cortex. Decreased phosphocreatine and NAA indicate energy metabolism deficit in brain cells; the latter also suggests the neuronal viability was inhibited. Decreased glutamate and glutamine may suggest the neuron-glial integrity was implicated by chronic SI. These neurochemical and biochemical changes may contribute to the SI-induced behavioral abnormalities including a high level of anxiety, social interaction deficit, and impaired spatial working memory shown in this study.

Keywords: Hippocampus; Neuron-glial integrity; Neuronal viability; Oxidative stress; Social isolation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Catalase / metabolism
  • Cerebral Cortex / metabolism
  • Energy Metabolism*
  • Female
  • Glutamic Acid / metabolism*
  • Glutamine / metabolism*
  • Glutathione Peroxidase / metabolism
  • Hippocampus / metabolism*
  • Hydrogen Peroxide / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Oxidative Stress*
  • Phosphocreatine / metabolism
  • Prefrontal Cortex / metabolism
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Social Isolation / psychology*
  • Superoxide Dismutase / metabolism


  • Phosphocreatine
  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate
  • Hydrogen Peroxide
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase