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

Abstract

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.

Effects of Activation and Blockade of Serotonin 5-HT1A Receptors on the Immune Response in Rats Selected for Different Levels of Aggressiveness

“…Excessive aggression is a symptom in a variety of neuropsychiatric disorders, such as schizophrenia, depression, anxiety disorder, and substance abuse [1]- [4], which have long been known to be associated with immune dysfunctions [5]- [8]. Consistent with clinical observations, data obtained on the basis of several animal models (isolation housing, social interactions or genetic predisposition) have indicated that aggressive behavior is accompanied with altered immune reactivity [9]- [22].…”

Comparative mRNA analysis of behavioral and genetic mouse models of aggression

“…This pathway is essential in regulating cellular processes such as apoptosis, differentiation, immunity, and stress responses. Activating stimuli of the NF-kB pathway include interleukin 1 and tumor necrosis factor (TNF), both of which are associated with aggression [Patel et al, 2010]. Previous studies on rat have reported an association between MAPK and increased aggression scores in rat [DeMar et al, 2006;Frey et al, 2006].…”

Translating the evidence for gene association with depression into mouse models of depression-relevant behaviour: Current limitations and future potential

“…Mice that were null mutant for Tnfr1 also exhibited decreased immobility in both the FST and TST, relative to WT (Kaster et al, 2012). Mice that were null mutant for Tnfr1 and Tnfr2 exhibited reduced anxiety in the light-dark box test (and reduced social aggression in the resident-intruder test), relative to WT (Patel et al, 2010).…”