Lack of aggression and anxiolytic-like behavior in TNF receptor (TNF-R1 and TNF-R2) deficient mice

The mechanisms underlying violence and aggression and its control remain poorly understood. Using the resident-intruder paradigm, we have discovered that resident mice with combined deletion of TNF receptor type 1 (TNF-R1) and type 2 (TNF-R2) genes show a striking absence of aggressive behavior, which includes fighting, sideways postures, and tail rattling. In parallel, resident TNF-R1 and TNF-R2 knockout mice show an increase in non-aggressive exploration of the intruder mice. Given the relationship between aggression and anxiety, we also measured anxiety-related behavior, as reflected by performance in the Open Field and the Light-Dark Choice Test. Compared with wild type mice, TNF-R1 and TNF-R2 deficient mice spent significantly more time and showed increased movement in the center of the Open Field and in the illuminated compartment of the light-dark box, suggesting an anxiolytic-like profile. Together, these data show that combined deletion of TNF-R1 and TNF-R2 results in a striking absence of aggressive behavior, an increase in non-aggressive exploration, and anxiolytic-like effects. These findings identify potent roles for TNF in regulating aggression and anxiety-related behavior, and suggest that TNF receptor signaling tonically modulates activity in brain regions underlying these behaviors.