title: Distinct Circuits Underlie the Effects of 5-HT1B Receptors on Aggression and Impulsivity.
abstract: Impulsive and aggressive behaviors are both modulated by serotonergic signaling, specifically through the serotonin 1B receptor (5-HT1BR). 5-HT1BR knockout mice show increased aggression and impulsivity, and 5-HT1BR polymorphisms are associated with aggression and drug addiction in humans. To dissect the mechanisms by which the 5-HT1BR affects these phenotypes, we developed a mouse model to spatially and temporally regulate 5-HT1BR expression. Our results demonstrate that forebrain 5-HT1B heteroreceptors expressed during an early postnatal period contribute to the development of the neural systems underlying adult aggression. However, distinct heteroreceptors acting during adulthood are involved in mediating impulsivity. Correlating with the impulsivity, dopamine in the nucleus accumbens is elevated in the absence of 5-HT1BRs and normalized following adult rescue of the receptor. Overall, these data show that while adolescent expression of 5-HT1BRs influences aggressive behavior, a distinct set of 5-HT1B receptors modulates impulsive behavior during adulthood.
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Division of Integrative Neuroscience, the New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Nautiyal
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo 160 8582, Japan.
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Barr
authors.affiliation: Université Paris-Sud, INSERM UMR-S 1178, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry 92296, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Tritschler
authors.affiliation: Université Paris-Sud, INSERM UMR-S 1178, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry 92296, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Dantec
authors.affiliation: Université Paris-Sud, INSERM UMR-S 1178, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry 92296, France.
authors.forename: Denis J
authors.initials: DJ
authors.lastname: David
authors.affiliation: Université Paris-Sud, INSERM UMR-S 1178, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry 92296, France.
authors.forename: Alain M
authors.initials: AM
authors.lastname: Gardier
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Division of Integrative Neuroscience, the New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Blanco
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Division of Integrative Neuroscience, the New York State Psychiatric Institute, New York, NY 10032, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA. Electronic address: rh95@columbia.edu.
authors.forename: René
authors.initials: R
authors.lastname: Hen
authors.affiliation: Department of Psychiatry, Translational Neuroscience Program, Center for Neuroscience Program, Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: ahmarise@upmc.edu.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Ahmari
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000374:Aggression / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology* / Q000254:growth & development / Q000378:metabolism; D002755:Choice Behavior / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007175:Impulsive Behavior / Q000502:physiology*; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D010869:Pindolol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000493:pharmacokinetics
chemical_list: D000199:Actins; D018765:Dopamine Uptake Inhibitors; D007456:Iodine Isotopes; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D012702:Serotonin Antagonists; D012701:Serotonin; C047975:cyanopindolol; C043425:vanoxerine; D010869:Pindolol; D004318:Doxycycline; D004298:Dopamine