Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice

Noelia V. Weisstaub; Mingming Zhou; Alena Lira; Evelyn Lambe; Javier González-Maeso; Jean Pierre Hornung; Etienna Sibille; Mark Underwood; Shigeyoshi Itohara; William T. Dauer; Mark S. Ansorge; Emanuela Morelli; J. John Mann; Miklos Toth; George Aghajanian; Stuart C. Sealfon; René Hen; Jay A. Gingrich

doi:10.1126/science.1123432

Cortical 5-HT_2A receptor signaling modulates anxiety-like behaviors in mice

Noelia V. Weisstaub, Mingming Zhou, Alena Lira, Evelyn Lambe, Javier González-Maeso, Jean Pierre Hornung, Etienna Sibille, Mark Underwood, Shigeyoshi Itohara, William T. Dauer, Mark S. Ansorge, Emanuela Morelli, J. John Mann, Miklos Toth, George Aghajanian, Stuart C. Sealfon, René Hen, Jay A. Gingrich

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353 Scopus citations

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.

Original language	English (US)
Pages (from-to)	536-540
Number of pages	5
Journal	Science
Volume	313
Issue number	5786
DOIs	https://doi.org/10.1126/science.1123432
State	Published - Jul 28 2006
Externally published	Yes

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Weisstaub, N. V., Zhou, M., Lira, A., Lambe, E., González-Maeso, J., Hornung, J. P., Sibille, E., Underwood, M., Itohara, S., Dauer, W. T., Ansorge, M. S., Morelli, E., Mann, J. J., Toth, M., Aghajanian, G., Sealfon, S. C., Hen, R., & Gingrich, J. A. (2006). Cortical 5-HT_2A receptor signaling modulates anxiety-like behaviors in mice. Science, 313(5786), 536-540. https://doi.org/10.1126/science.1123432

Weisstaub, NV, Zhou, M, Lira, A, Lambe, E, González-Maeso, J, Hornung, JP, Sibille, E, Underwood, M, Itohara, S, Dauer, WT, Ansorge, MS, Morelli, E, Mann, JJ, Toth, M, Aghajanian, G, Sealfon, SC, Hen, R & Gingrich, JA 2006, 'Cortical 5-HT_2A receptor signaling modulates anxiety-like behaviors in mice', Science, vol. 313, no. 5786, pp. 536-540. https://doi.org/10.1126/science.1123432

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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.",

author = "Weisstaub, {Noelia V.} and Mingming Zhou and Alena Lira and Evelyn Lambe and Javier Gonz{\'a}lez-Maeso and Hornung, {Jean Pierre} and Etienna Sibille and Mark Underwood and Shigeyoshi Itohara and Dauer, {William T.} and Ansorge, {Mark S.} and Emanuela Morelli and Mann, {J. John} and Miklos Toth and George Aghajanian and Sealfon, {Stuart C.} and Ren{\'e} Hen and Gingrich, {Jay A.}",

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doi = "10.1126/science.1123432",

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AU - Weisstaub, Noelia V.

AU - Zhou, Mingming

AU - Lira, Alena

AU - Lambe, Evelyn

AU - González-Maeso, Javier

AU - Hornung, Jean Pierre

AU - Sibille, Etienna

AU - Underwood, Mark

AU - Itohara, Shigeyoshi

AU - Dauer, William T.

AU - Ansorge, Mark S.

AU - Morelli, Emanuela

AU - Mann, J. John

AU - Toth, Miklos

AU - Aghajanian, George

AU - Sealfon, Stuart C.

AU - Hen, René

AU - Gingrich, Jay A.

PY - 2006/7/28

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N2 - 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.

AB - 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.

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Cortical 5-HT_2A receptor signaling modulates anxiety-like behaviors in mice

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