title: A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression-Related Behaviors.
abstract: The effects of serotonin (5-HT) on anxiety and depression are mediated by a number of 5-HT receptors, including autoreceptors that act to inhibit 5-HT release. While the majority of anxiety and depression-related research has focused on the 5-HT1Areceptor, the 5-HT1Breceptor has a lesser known role in modulating emotional behavior. 5-HT1Breceptors are inhibitory GPCRs located on the presynaptic terminal of both serotonin and non-serotonin neurons, where they act to inhibit neurotransmitter release. The autoreceptor population located on the axon terminals of 5-HT neurons is a difficult population to study due to their diffuse localization throughout the brain that overlaps with 5-HT1Bheteroreceptors (receptors located on non-serotonergic neurons). In order to study the contribution of 5-HT1Bautoreceptors to anxiety and depression-related behaviors, we developed a genetic mouse model that allows for selective ablation of 5-HT1Bautoreceptors. Mice lacking 5-HT1Bautoreceptors displayed the expected increases in extracellular serotonin levels in the ventral hippocampus following administration of a selective serotonin reuptake inhibitor. In behavioral studies, they displayed decreased anxiety-like behavior in the open field and antidepressant-like effects in the forced swim and sucrose preference tests. These results suggest that strategies aimed at blocking 5-HT1Bautoreceptors may be useful for the treatment of anxiety and depression.
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|Division of Integrative Neuroscience, The New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Nautiyal
authors.affiliation: Université Paris-Saclay, University Paris-Sud, Faculté de Pharmacie, CESP, INSERM UMRS1178, Chatenay-Malabry, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Tritschler
authors.affiliation: Department of Psychiatry, Translational Neuroscience Program, Center for Neuroscience Program, Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Ahmari
authors.affiliation: Université Paris-Saclay, University Paris-Sud, Faculté de Pharmacie, CESP, INSERM UMRS1178, Chatenay-Malabry, France.
authors.forename: Denis J
authors.identifier: 0000-0002-0506-6688
authors.initials: DJ
authors.lastname: David
authors.affiliation: Université Paris-Saclay, University Paris-Sud, Faculté de Pharmacie, CESP, INSERM UMRS1178, Chatenay-Malabry, France.
authors.forename: Alain M
authors.initials: AM
authors.lastname: Gardier
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|Division of Integrative Neuroscience, The New York State Psychiatric Institute, New York, NY, USA.|Department of Neuroscience, Columbia University, New York, NY, USA.
authors.forename: René
authors.initials: R
authors.lastname: Hen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D017660:Autoreceptors / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005518:Food Preferences / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010869:Pindolol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D044302:Receptor, Serotonin, 5-HT1B / Q000172:deficiency* / Q000235:genetics; D044263:Receptors, Serotonin, 5-HT1 / Q000235:genetics / Q000378:metabolism; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism
chemical_list: D017660:Autoreceptors; D007456:Iodine Isotopes; D044302:Receptor, Serotonin, 5-HT1B; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C047975:cyanopindolol; D010869:Pindolol