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

J. Halász, M. Tóth, E. Mikics, E. Hrabovszky, Boglarka Barsy, Beata Barsvari, J. Haller

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)271-278
Number of pages8
JournalBiological Psychiatry
Volume63
Issue number3
DOIs
Publication statusPublished - Feb 1 2008

Fingerprint

Aggression
Neurons
Violence
L 703606
Anxiety
Depression
Bites and Stings
Locomotion
Amygdala
Human Body
Brain

Keywords

  • Aggression
  • amygdala
  • glucocorticoid
  • NK1 receptor
  • Substance P
  • violence

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

The Effect of Neurokinin1 Receptor Blockade on Territorial Aggression and in a Model of Violent Aggression. / Halász, J.; Tóth, M.; Mikics, E.; Hrabovszky, E.; Barsy, Boglarka; Barsvari, Beata; Haller, J.

In: Biological Psychiatry, Vol. 63, No. 3, 01.02.2008, p. 271-278.

Research output: Contribution to journalArticle

@article{0b5072e3a33f4c27977bafd9eff253fe,
title = "The Effect of Neurokinin1 Receptor Blockade on Territorial Aggression and in a Model of Violent Aggression",
abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: 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.",
keywords = "Aggression, amygdala, glucocorticoid, NK1 receptor, Substance P, violence",
author = "J. Hal{\'a}sz and M. T{\'o}th and E. Mikics and E. Hrabovszky and Boglarka Barsy and Beata Barsvari and J. Haller",
year = "2008",
month = "2",
day = "1",
doi = "10.1016/j.biopsych.2007.04.022",
language = "English",
volume = "63",
pages = "271--278",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "3",

}

TY - JOUR

T1 - The Effect of Neurokinin1 Receptor Blockade on Territorial Aggression and in a Model of Violent Aggression

AU - Halász, J.

AU - Tóth, M.

AU - Mikics, E.

AU - Hrabovszky, E.

AU - Barsy, Boglarka

AU - Barsvari, Beata

AU - Haller, J.

PY - 2008/2/1

Y1 - 2008/2/1

N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

KW - Aggression

KW - amygdala

KW - glucocorticoid

KW - NK1 receptor

KW - Substance P

KW - violence

UR - http://www.scopus.com/inward/record.url?scp=37849054548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37849054548&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2007.04.022

DO - 10.1016/j.biopsych.2007.04.022

M3 - Article

VL - 63

SP - 271

EP - 278

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 3

ER -