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.