Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Cortical 5-HT2A Receptor Signaling Modulates Anxiety-Like Behaviors in Mice
Noelia V. Weisstaub,1,3Mingming Zhou,2Alena Lira,2Evelyn Lambe,6*Javier González-Maeso,7Jean-Pierre Hornung,8Etienne Sibille,1Mark Underwood,2Shigeyoshi Itohara,9William T. Dauer,5Mark S. Ansorge,2,3Emanuela Morelli,2,3J. John Mann,2Miklos Toth,10George Aghajanian,6Stuart C. Sealfon,7René Hen,2,4Jay A. Gingrich2,3
Serotonin [5-hydroxytryptamine (5-HT)] neurotransmission inthe central nervous system modulates depression and anxiety-relatedbehaviors in humans and rodents, but the responsible downstreamreceptors remain poorly understood. We demonstrate that globaldisruption of 5-HT2A receptor (5HT2AR) signaling in mice reducesinhibition in conflict anxiety paradigms without affecting fear-conditionedand depression-related behaviors. Selective restoration of 5HT2ARsignaling to the cortex normalized conflict anxiety behaviors.These findings indicate a specific role for cortical 5HT2ARfunction in the modulation of conflict anxiety, consistent withmodels 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
Role of GSK3{beta} in behavioral abnormalities induced by serotonin deficiency.
J.-M. Beaulieu, X. Zhang, R. M. Rodriguiz, T. D. Sotnikova, M. J. Cools, W. C. Wetsel, R. R. Gainetdinov, and M. G. Caron (2008)
PNAS
105, 1333-1338
|Abstract »|Full Text »|PDF »
Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: Role of corticosterone-mediated apical dendritic atrophy.
R.H. Belmaker and G. Agam (2008)
N. Engl. J. Med.
358, 55-68
|Full Text »|PDF »
Serotonin Activates the Hypothalamic-Pituitary-Adrenal Axis via Serotonin 2C Receptor Stimulation.
L. K. Heisler, N. Pronchuk, K. Nonogaki, L. Zhou, J. Raber, L. Tung, G. S. H. Yeo, S. O'Rahilly, W. F. Colmers, J. K. Elmquist, et al. (2007)
J. Neurosci.
27, 6956-6964
|Abstract »|Full Text »|PDF »
Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex.
J.-C. Beique, M. Imad, L. Mladenovic, J. A. Gingrich, and R. Andrade (2007)
PNAS
104, 9870-9875
|Abstract »|Full Text »|PDF »
Serotonergic Modulation of Plasticity of the Auditory Cortex Elicited by Fear Conditioning.
Deficiency in Na,K-ATPase {alpha} Isoform Genes Alters Spatial Learning, Motor Activity, and Anxiety in Mice.
A. E. Moseley, M. T. Williams, T. L. Schaefer, C. S. Bohanan, J. C. Neumann, M. M. Behbehani, C. V. Vorhees, and J. B Lingrel (2007)
J. Neurosci.
27, 616-626
|Abstract »|Full Text »|PDF »
Anxious About Where Serotonin Works?.
(2006)
Journal Watch Psychiatry
2006, 2
|Full Text »
Current address: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA. 
To whom correspondence should be addressed. E-mail: 
