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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Available from: Stuart C Sealfon, Oct 09, 2015
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    • "Normal depressive-like behavior in the FST and TST Impaired facilitation of synaptic activity in PFC Weisstaub et al., 2006; Beique et al., 2007 -Decreased anxietylike behavior TPH2 Tryptophan hydroxilase 2 Kim et al., 2009 Tph2 À / À ; "
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    European journal of pharmacology 03/2015; 759. DOI:10.1016/j.ejphar.2015.03.039 · 2.53 Impact Factor
    • "In general, these studies support the notion that early life adverse experience is a major risk factor for anxiety development (Benekareddy et al. 2011). Serotonergic neurotransmission is known to be related to anxiety (Gross and Hen 2004), and serotonin type 2 (5-HT2) receptors have been implicated as possible targets to modulate anxiety behavior (Weisstaub et al 2006). "
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    Advances in neurobiology 01/2015; 10:121-47. DOI:10.1007/978-1-4939-1372-5_7
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    • "Preclinical study 2.1.1. Animals Adult male 5-HT 2A R mutants (Htr2a −/− mice) and wild-type mice (Htr2a +/+ mice) (Weisstaub et al., 2006 "
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    ABSTRACT: An association between serotonin 2A receptor (5-HT2AR), encoded by HTR2A gene, and major depressive disorder (MDD) has been suggested. Here, we combined preclinical and ecological clinical approaches to explore the impact of impaired 5-HT2AR-mediated transmission on MDD or anxio-depressive-like phenotype in mice. Htr2a knock-out mice (Htr2a-/- ) and wild-type mice were compared for the ability of chronic corticosterone to elicit some anxio-depressive-like phenotype in three behavioral paradigms (elevated plus maze, tail suspension test and splash test). Accordingly, two single nucleotide polymorphisms of the HTR2A gene (rs6314 ie His452Tyr and rs6313 ie 102C/T), which specific allelic variants may decrease 5-HT2AR-mediated transmission (as in Htr2a-/-mice), were studied in a sample of 485 Caucasian patients with MDD. In response to chronic corticosterone exposure, Htr2a-/- mice displayed more pronounced anxiodepressive-like phenotype than wild-type mice, as shown by a significant higher “emotionality score” (p < 0.01). In patients, the C allele of rs6313 was more frequent in depressed patients (p = 0.019) and was also associated with a more severe major depressive episode (p = 0.03). This translational and ecological study involving constitutive Htr2a-/- knock-out mice and related SNPs in depressed patients suggests that a lower neurotransmission at the 5-HT2AR may favor the susceptibility and severity of MDE. It also suggests that specific allelic variants of the rs6313 and rs6314 may reduce 5-HT2AR-mediated transmission.
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