Effects of Various Interval Hypoxic Training Regimens in Experimental Models of Anxious-Depressive States in Rats

The development of non-drug-based methods for correcting stress-induced disorders and improving adaptation to stress remains an urgent task in physiology and has great translational potential. We have previously proposed methods for hypoxic hypobaric preconditioning and remote ischemic conditioning, which are effective in this regard. The aim of the present work was to transfer the principles of preconditioning to develop normobaric hypoxic interval training (HIT) approaches. The effects of five new HIT regimens (three × 5-min hypoxia sessions of 16% O₂ per day, three sessions of 12% O₂, seven sessions of 12% O₂, 15 sessions of 12% O₂, and three sessions of 9% O₂) were studied in experimental models of depression and post-traumatic stress disorder in rats. A high-intensity preconditioning regimen of 3 × 9% O₂ had the most marked antidepressant and anxiolytic effects in models of both pathologies. When the level of hypoxia was reduced to 12% O₂, HIT regimens partially retained their efficacy as the number of sessions increased. The training regimen with the longest duration, i.e., 15 × 12% O₂, was effective in correcting the formation of experimental depression. The transitional regimen of 7 x 12% O₂ had an anxiolytic effect, while the moderate-intensity preconditioning regimen of 3 x 12% O₂ demonstrated both antidepressant and anxiolytic effects. These results indicate that the intensity of hypoxic exposure had the greatest effect on efficacy. A decrease in intensity to 16% O₂ led to weakening or loss of stress-protective properties. In relation to the 3 × 9% O₂ regimen being the most promising, there will be value in carrying out further research to identify the molecular mechanisms mediating its stress-protective and anxiolytic effects.