title: Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice.
abstract: Serotonin [5-hydroxytryptamine (5-HT)] neurotransmission in the central nervous system modulates depression and anxiety-related behaviors in humans and rodents, but the responsible downstream receptors remain poorly understood. We demonstrate that global disruption of 5-HT2A receptor (5HT2AR) signaling in mice reduces inhibition in conflict anxiety paradigms without affecting fear-conditioned and depression-related behaviors. Selective restoration of 5HT2AR signaling to the cortex normalized conflict anxiety behaviors. These findings indicate a specific role for cortical 5HT2AR function in the modulation of conflict anxiety, consistent with models of cortical, "top-down" influences on risk assessment.
authors.affiliation: Department of Biology, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Noelia V
authors.initials: NV
authors.lastname: Weisstaub
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhou
authors.forename: Alena
authors.initials: A
authors.lastname: Lira
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lambe
authors.forename: Javier
authors.initials: J
authors.lastname: González-Maeso
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hornung
authors.forename: Etienne
authors.initials: E
authors.lastname: Sibille
authors.forename: Mark
authors.initials: M
authors.lastname: Underwood
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: William T
authors.initials: WT
authors.lastname: Dauer
authors.forename: Mark S
authors.initials: MS
authors.lastname: Ansorge
authors.forename: Emanuela
authors.initials: E
authors.lastname: Morelli
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: Miklos
authors.initials: M
authors.lastname: Toth
authors.forename: George
authors.initials: G
authors.lastname: Aghajanian
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Sealfon
authors.forename: René
authors.initials: R
authors.lastname: Hen
authors.forename: Jay A
authors.initials: JA
authors.lastname: Gingrich
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000378:metabolism*; D003213:Conditioning, Psychological; D003220:Conflict, Psychological; D003863:Depression / Q000503:physiopathology; D005106:Exploratory Behavior; D005239:Fear; D008032:Limbic System / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D012309:Risk-Taking; D012701:Serotonin / Q000502:physiology; D015398:Signal Transduction; D009435:Synaptic Transmission
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017981:Receptors, Neurotransmitter; D012701:Serotonin