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Science 313 (5786): 536-540

Copyright © 2006 by the American Association for the Advancement of Science

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{dagger} 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{ddagger}

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.

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.

{dagger} Current address: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA.

{ddagger} To whom correspondence should be addressed. E-mail: jag46{at}

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