title: Serotonin-1A autoreceptors are necessary and sufficient for the normal formation of circuits underlying innate anxiety.
abstract: Identifying the factors contributing to the etiology of anxiety and depression is critical for the development of more efficacious therapies. Serotonin (5-HT) is intimately linked to both disorders. The inhibitory serotonin-1A (5-HT(1A)) receptor exists in two separate populations with distinct effects on serotonergic signaling: (1) an autoreceptor that limits 5-HT release throughout the brain and (2) a heteroreceptor that mediates inhibitory responses to released 5-HT. Traditional pharmacologic and transgenic strategies have not addressed the distinct roles of these two receptor populations. Here we use a recently developed genetic mouse system to independently manipulate 5-HT(1A) autoreceptor and heteroreceptor populations. We show that 5-HT(1A) autoreceptors act to affect anxiety-like behavior. In contrast, 5-HT(1A) heteroreceptors affect responses to forced swim stress, without effects on anxiety-like behavior. Together with our previously reported work, these results establish distinct roles for the two receptor populations, providing evidence that signaling through endogenous 5-HT(1A) autoreceptors is necessary and sufficient for the establishment of normal anxiety-like behavior.
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York 10032, USA.
authors.forename: Jesse W
authors.initials: JW
authors.lastname: Richardson-Jones
authors.forename: Caryne P
authors.initials: CP
authors.lastname: Craige
authors.forename: Thanh H
authors.initials: TH
authors.lastname: Nguyen
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
authors.forename: Alain M
authors.initials: AM
authors.lastname: Gardier
authors.forename: Alex
authors.initials: A
authors.lastname: Dranovsky
authors.forename: Denis J
authors.initials: DJ
authors.lastname: David
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Guiard
authors.forename: Sheryl G
authors.initials: SG
authors.lastname: Beck
authors.forename: René
authors.initials: R
authors.lastname: Hen
authors.forename: E David
authors.initials: ED
authors.lastname: Leonardo
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001345:Autoradiography; D001522:Behavior, Animal / Q000502:physiology*; D002375:Catalepsy; D004594:Electrophysiology; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D009415:Nerve Net / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*
chemical_list: D044282:Receptor, Serotonin, 5-HT1A