Residing at high altitude may lead to reduced blood oxygen saturation in the brain and altered metabolism in frontal cortical brain areas, probably due to chronic hypobaric
hypoxia. These changes may underlie the increased rates of depression and suicidal behavior that have been associated with life at higher altitudes. To test the hypothesis that hypobaric
hypoxia is responsible for development of
mood disorders due to alterations in neurochemistry, we assessed depression-like behavior in parallel to levels of brain metabolites in rats housed at simulated altitude. 32 female Sprague Dawley rats were housed either in a hypobaric
hypoxia chamber at 10,000 ft of simulated altitude for 1 week or at local conditions (4500 ft of elevation in
Salt Lake City, Utah). Depression-like behavior was assessed using the forced swim test (FST) and levels of neurometabolites were estimated by in vivo
proton magnetic resonance spectroscopy in the frontal cortex, the striatum and the hippocampus at baseline and after a week of exposure to hypobaric
hypoxia. After
hypoxia exposure the animals demonstrated increased immobility behavior and shortened latency to immobility in the FST. Elevated ratios of myo-
inositol,
glutamate, and the sum of myo-
inositol and
glycine to total
creatine were observed in the frontal cortex of
hypoxia treated rats. A decrease in the ratio of
alanine to total
creatine was also noted. This study shows that
hypoxia induced alterations in frontal lobe brain metabolites, aggravated depression-like behavior and might be
a factor in increased rates of
psychiatric disorders observed in populations living at high altitudes.