Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice.
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.
Weisstaub
Noelia V
NV
Department of Biology, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.
Zhou
Mingming
M
Lira
Alena
A
Lambe
Evelyn
E
González-Maeso
Javier
J
Hornung
Jean-Pierre
JP
Sibille
Etienne
E
Underwood
Mark
M
Itohara
Shigeyoshi
S
Dauer
William T
WT
Ansorge
Mark S
MS
Morelli
Emanuela
E
Mann
J John
JJ
Toth
Miklos
M
Aghajanian
George
G
Sealfon
Stuart C
SC
Hen
René
R
Gingrich
Jay A
JA
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
D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017981:Receptors, Neurotransmitter; D012701:Serotonin