We studied the dynamics of the activation of the CREB and NF-κB transcription factors in areas of the rat brain after exposure to pathogenic psycho-emotional stress in the model of endogenous depression and the model of posttraumatic stress disorder (PTSD), as well as after application of hypoxic preconditioning, which prevents the formation of anxiety-depressive pathologies in these models. The development of anxiety-depressive pathology in both models was associated with reduced (10 times lower than the control maximum) or basal levels of the activating transcription factors CREB and NF-κB in the hippocampus and the neocortex. However, in the hypothalamus, NF-κB overactivation (up to an 18-fold increase above the control level) was detected in the model of depression. Therefore the lack of activation of these factors in the extra-hypothalamic areas of the brain may be a common component of the pathogenesis of both depression and PTSD, while NF-κB overactivation in the neurosecretory centers of the hypothalamus is obviously involved in the development of depressive conditions. Antidepressant and anxiolytic actions of hypoxic preconditioning were accompanied by a mild 2- to 6-fold increase in CREB and NF-κB levels in the neurons of the brain in both stress paradigms. Obviously, the maintenance of optimum activity of transcription factors in the neurons of the brain plays an important role in nonspecific compensatory processes that enhance the adaptive potential of the brain under stress conditions.