Stress enhances aggression in male rats with genetic stress hyper-reactivity.

The current study investigated stress-induced aggressive behavior in the resident-intruder test in males of the genetically stress hyper-reactive Wistar Kyoto More Immobile (WMI), and the nearly isogenic, control Wistar Kyoto Less Immobile (WLI) strains. Tests were carried out against same-age intruders during adolescence, and same-age and juvenile intruders in adulthood. In adolescence and adulthood, prior acute restraint stress decreased social interactions and decreased aggressive behaviors of adolescents and adult WLIs. However, prior stress precipitated aggression in the adult WMI males toward both same-age, and juvenile intruders compared with control WMIs and WLIs. Trunk blood levels of testosterone and androstenedione increased in stressed WLIs, but not in WMIs, suggesting no direct role of androgens in the increased aggression of WMIs. Expressions of aggression-relevant genes showed patterns commensurate with being causative in aggressive behavior. The methyl-CpG binding protein 2 was lower in the frontal cortex of control WMIs, and in the amygdala of stressed WMIs compared with their respective WLIs. Frontal cortex expression of vasopressin receptor 1a and serotonin transporter increased, solely in WMI males after stress. As behaviors were the same toward same-age and non-threatening juvenile intruders, the stress-induced increase in confrontational behavior of the adult WMI male was not because of enhanced fear or anxiety. These results suggest that genetic stress hyper-reactivity is a risk factor for stress-induced increases in aggression in males. Additionally, as known aggression-related genes showed expression patterns paralleling aggressive behavior, this model system could identify novel molecular pathways leading to stress-enhanced aggression.