Cortical 5-HT2A Receptor Signaling Modulates Anxiety-Like Behaviors in Mice
Noelia V. Weisstaub,1,3
Mingming Zhou,2
Alena Lira,2
Evelyn Lambe,6*
Javier González-Maeso,7
Jean-Pierre Hornung,8
Etienne Sibille,1
Mark Underwood,2
Shigeyoshi Itohara,9
William T. Dauer,5
Mark S. Ansorge,2,3
Emanuela Morelli,2,3
J. John Mann,2
Miklos Toth,10
George Aghajanian,6
Stuart C. Sealfon,7
René Hen,2,4
Jay A. Gingrich2,3
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.
1 Department of Biology, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.
2 Department of Psychiatry, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.
3 Sackler Institute Laboratories, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.
4 Center for Neurobiology and Behavior, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.
5 Department of Neurology, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.
6 Department of Psychiatry, Yale University, New Haven, CT 06520, USA.
7 Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
8 Institut de Biologie Cellulaire et de Morphologie, Université de Lausanne, Lausanne, Switzerland.
9 Laboratory for Behavioral Genetics, Riken Brain Science Institute, Wako City, Japan
10 Department of Pharmacology, Cornell University Medical Center, New York, NY 10021, USA.
* Present address: Department of Physiology, University of Toronto, Toronto ON, M5S1A8, Canada.
Current address: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA.
To whom correspondence should be addressed. E-mail: jag46{at}columbia.edu
