Stress-reaction developed after exposure to stressors of different natures, increases the level of DNA damage in cells of target organs, including the central nervous system. However, the time of stressing exposure needed to induce genome destabilization in different brain areas and individual differences in animals defining their brain cell genome response to stressors is unclear. In this research, we show that acute stressors (2-h immobilization or 13-min emotional-painful stressor) increase the level of DNA damage in at least one of the brain regions studied: the prefrontal cortex, hippocampus, and amygdala in rat strains with the high or low threshold of nerve tibialis excitability, and non-selected Wistar rats. The results reveal the interstrain differences in the genome response to acute stressors of each brain area, different from the repeated emotional-painful stressor effects shown earlier.