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

University of Lausanne, Lausanne, Vaud, Switzerland
Science (Impact Factor: 33.61). 08/2006; 313(5786):536-40. DOI: 10.1126/science.1123432
Source: PubMed


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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    • "Inhibitory effects of 5-HT on GABA mIPSC frequency suggested that 5-HT receptors were acting presynaptically. Combining pharmacological tools with mice lacking 5-HT 2A receptors (5-HT 2A /- ; Weisstaub et al., 2006), we described inhibitory 5-HT 1A receptors at presynaptic terminals from 5-HT 2A -/-mice. The lower inhibitory effects of 5-HT 100 μM puff in VB neurons from WT mice suggested that 5-HT 2A receptors could counteract the inhibitory actions of 5-HT 1A. "
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