Normobaric oxygen treatment in a depression-like model in male and female rats - Safety, behavioral benefits, and modulation of serotonin and inflammatory markers.

Depression is growingly recognized as a major public health problem. A large body of data supports the notion that alterations in oxygen (O2) supply to the brain contribute to the pathophysiology of depression. We examined safety and efficacy parameters of chronic normobaric O2 treatment (NO2T) in naïve and stress-subjected "depressed" rats. Safety parameters - including hematological, biochemical, and respiratory - were tested in naïve rats. Other groups of rats were subjected to a stress protocol and then treated with NO2T (40 % O2) for four weeks. Post-stress rats underwent behavioral assessments and evaluations of brain inflammatory mediators and serotonin levels. We found that: i) NO2T was associated with a high tolerability profile in naïve rats; ii) NO2T produced a potent antidepressant-like effect as well as other positive behavioral outcomes in post-stress rats; and, iii) NO2T decreased inflammatory components and kynurenine, and increased serotonin levels in the frontal cortex and hippocampus of post-stress rats. This study provides evidence for the efficacy and safety of NO2T in a rodent model of depression, highlighting its potential as a novel antidepressant treatment. Further research is needed to explore long-term effects and underlying mechanisms.