Differential role of the 5-HT1A receptor in aggressive and non-aggressive mice: an across-strain comparison

Doretta Caramaschi, Sietse F de Boer, Jaap M Koolhaas

Research output: Contribution to journalArticle (Academic Journal)peer-review

92 Citations (Scopus)

Abstract

Differential role of the 5-HT(1A) receptor in aggressive and non-aggressive mice: an across-strain comparison. PHYSIOL BEHAV 00(0) 000-000, 2006. According to the serotonin (5-HT)-deficiency hypothesis of aggression, highly aggressive individuals are characterized by low brain 5-HT neurotransmission. Key regulatory mechanisms acting on the serotonergic neuron involve the activation of the somatodendritic inhibitory 5-HT(1A) autoreceptor (short feedback loop) and/or the activation of postsynaptic 5-HT(1A) receptors expressed on neurons in cortico-limbic areas (long feedback loop). In this study, we examined whether low serotonin neurotransmission is associated with enhanced 5-HT(1A) (auto)receptor activity in highly aggressive animals. Male mice (SAL-LAL, TA-TNA, NC900-NC100) obtained through different artificial-selection breeding programs for aggression were observed in a resident-intruder test. The prefrontal cortex level of 5-HT and its metabolite 5-HIAA were determined by means of HPLC. The activity of the 5-HT(1A) receptors was assessed by means of the hypothermic response to the selective 5-HT(1A) agonists S-15535 (preferential autoreceptor agonist) and 8-OHDPAT (full pre- and postsynaptic receptor agonist). Highly aggressive mice had lower serotonin levels in the prefrontal cortex and two out of three aggressive strains had higher 5-HT(1A) (auto)receptor sensitivity. The results strengthen the validity of the serotonin-deficiency hypothesis of aggression and suggest that chronic exaggerated activity of the 5-HT(1A) receptor may be a causative link in the neural cascade of events leading to 5-HT hypofunction in aggressive individuals.

Original languageEnglish
Pages (from-to)590-601
Number of pages12
JournalPhysiology and Behavior
Volume90
Issue number4
DOIs
Publication statusPublished - 16 Mar 2007

Keywords

  • Aggression
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Body Temperature
  • Brain Chemistry
  • Male
  • Mice
  • Mice, Inbred Strains
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Serotonin Receptor Agonists
  • Species Specificity
  • Comparative Study
  • Journal Article

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