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

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.

Pubmed ID: 16873667


  • Weisstaub NV
  • Zhou M
  • Lira A
  • Lambe E
  • Gonz├ílez-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


Science (New York, N.Y.)

Publication Data

July 28, 2006

Associated Grants

  • Agency: NIMH NIH HHS, Id: KO8 MH01711
  • Agency: NIDA NIH HHS, Id: P01 DA12923

Mesh Terms

  • Animals
  • Anxiety
  • Cerebral Cortex
  • Conditioning (Psychology)
  • Conflict (Psychology)
  • Depression
  • Exploratory Behavior
  • Fear
  • Limbic System
  • Mice
  • Mice, Knockout
  • Patch-Clamp Techniques
  • Periaqueductal Gray
  • Prosencephalon
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Neurotransmitter
  • Risk-Taking
  • Serotonin
  • Signal Transduction
  • Synaptic Transmission