title: Differential role of the 5-HT1A receptor in aggressive and non-aggressive mice: an across-strain comparison.
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.
authors.affiliation: Department of Behavioral Physiology, University of Groningen, Haren, 9751 AA, The Netherlands. D.Caramaschi@rug.nl
authors.forename: Doretta
authors.initials: D
authors.lastname: Caramaschi
authors.forename: Sietse F
authors.initials: SF
authors.lastname: de Boer
authors.forename: Jaap M
authors.initials: JM
authors.lastname: Koolhaas
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013045:Species Specificity
chemical_list: D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin