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Cortical 5-HT2A Receptor Signaling Modulates Anxiety-Like Behaviors in Mice

Science  28 Jul 2006:
Vol. 313, Issue 5786, pp. 536-540
DOI: 10.1126/science.1123432

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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.

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