The Effect of Neurokinin1 Receptor Blockade on Territorial Aggression and in a Model of Violent Aggression

Abstract

Neurokinin1 (NK1) receptor blockers were recently proposed for the treatment of anxiety and depression. Disparate data suggest that NK1 receptors are also involved in the control of aggressiveness, but their role is poorly known. We evaluated the aggression-induced activation of NK1 neurons by double-labeling brain sections for NK1 receptors and c-Fos in two laboratory models of aggression. We also studied the effects of the NK1 antagonist L-703,606 in these models. Aggressive encounters activated a large number of NK1 receptor-expressing neurons in areas relevant for aggression control. The activation was aggression-specific, because the effects of psychosocial encounters (that allowed sensory but not physical contacts) were markedly weaker. In the medial amygdala, the activation of neurons expressing NK1 receptors showed a marked positive correlation with the occurrence of violent attacks. In resident/intruder conflicts, NK1 blockade lowered the number of hard bites, without affecting milder forms of attack. In the model of violent aggression, attacks on vulnerable body parts of opponents (the main indicators of violence in this model) were decreased to the levels seen in control subjects. Autonomic deficits seen in the model of violent aggression were also ameliorated. The effects of the compound were not secondary to changes in locomotion or in the behavior of intruders. Our data show that neurons expressing NK1 receptors are involved in the control of aggressiveness, especially in the expression of violent attacks. This suggests that NK1 antagonists-beyond anxiety and depression-might also be useful in the treatment of aggressiveness and violence.