title: Suppression of serotonin neuron firing increases aggression in mice.
abstract: Numerous studies link decreased serotonin metabolites with increased impulsive and aggressive traits. However, although pharmacological depletion of serotonin is associated with increased aggression, interventions aimed at directly decreasing serotonin neuron activity have supported the opposite association. Furthermore, it is not clear if altered serotonin activity during development may contribute to some of the observed associations. Here, we used two pharmacogenetic approaches in transgenic mice to selectively and reversibly reduce the firing of serotonin neurons in behaving animals. Conditional overexpression of the serotonin 1A receptor (Htr1a) in serotonin neurons showed that a chronic reduction in serotonin neuron firing was associated with heightened aggression. Overexpression of Htr1a in adulthood, but not during development, was sufficient to increase aggression. Rapid suppression of serotonin neuron firing by agonist treatment of mice expressing Htr1a exclusively in serotonin neurons also led to increased aggression. These data confirm a role of serotonin activity in setting thresholds for aggressive behavior and support a direct association between low levels of serotonin homeostasis and increased aggression.
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory, 00015 Monterotondo, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Audero
authors.forename: Boris
authors.initials: B
authors.lastname: Mlinar
authors.forename: Gilda
authors.initials: G
authors.lastname: Baccini
authors.forename: Zhiva K
authors.initials: ZK
authors.lastname: Skachokova
authors.forename: Renato
authors.initials: R
authors.lastname: Corradetti
authors.forename: Cornelius
authors.initials: C
authors.lastname: Gross
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000633:toxicity; D000200:Action Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000374:Aggression / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000473:pathology; D001345:Autoradiography; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D007035:Hypothermia / Q000139:chemically induced; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D011903:Raphe Nuclei / Q000166:cytology*; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D059326:Serotonergic Neurons / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D017366:Serotonin Receptor Agonists / Q000633:toxicity; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000235:genetics
chemical_list: C416045:4-iodo-N-(2-(4-(methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinylbenzamide; D007456:Iodine Isotopes; D010879:Piperazines; D011725:Pyridines; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; C493231:Slc6a4 protein, mouse; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase