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

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

92 Citaten (Scopus)
421 Downloads (Pure)

Samenvatting

Differential role of the 5-HT1A 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-HT1A autoreceptor (short feedback loop) and/or the activation of postsynaptic 5-HT1A 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 I A (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-HT1A receptors was assessed by means of the hypothermic response to the selective 5-HT1A 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-HT1A (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 I A receptor may be a causative link in the neural cascade of events leading to 5-HT hypofunction in aggressive individuals. (c) 2007 Elsevier Inc. All rights reserved.

Originele taal-2English
Pagina's (van-tot)590-601
Aantal pagina's12
TijdschriftPhysiology & Behavior
Volume90
Nummer van het tijdschrift4
DOI's
StatusPublished - 16-mrt-2007

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