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Yinan DU, Zhiwei LI, Yukui ZHAO, Jing HAN, Weiping HU, Zhiqiang LIU. Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions[J]. Journal of Zhejiang University Science B, 2024, 25(1): 23-37.
@article{title="Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions",
author="Yinan DU, Zhiwei LI, Yukui ZHAO, Jing HAN, Weiping HU, Zhiqiang LIU",
journal="Journal of Zhejiang University Science B",
volume="25",
number="1",
pages="23-37",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200642"
}
%0 Journal Article
%T Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions
%A Yinan DU
%A Zhiwei LI
%A Yukui ZHAO
%A Jing HAN
%A Weiping HU
%A Zhiqiang LIU
%J Journal of Zhejiang University SCIENCE B
%V 25
%N 1
%P 23-37
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200642
TY - JOUR
T1 - Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions
A1 - Yinan DU
A1 - Zhiwei LI
A1 - Yukui ZHAO
A1 - Jing HAN
A1 - Weiping HU
A1 - Zhiqiang LIU
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 1
SP - 23
EP - 37
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200642
Abstract: 5-Hydroxytryptamine (5-HT) type 3 receptor (5-HT3R) is the only type of ligand-gated ion channel in the 5-HT receptor family. Through the high permeability of Na+, K+, and Ca2+ and activation of subsequent voltage-gated calcium channels (VGCCs), 5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system (CNS). 5-HT3Rs are widely expressed in the medial prefrontal cortex (mPFC), amygdala (AMYG), hippocampus (HIP), periaqueductal gray (PAG), and other brain regions closely associated with anxiety reactions. They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions. 5-HT3Rs mediate the activation of the cholecystokinin (CCK) system in the AMYG, and the γ-aminobutyric acid (GABA) “disinhibition” mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons (IINs). In contrast, a 5-HT3R-induced GABA “disinhibition” mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects. 5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG. This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs. However, given the circuit specific modulation of 5-HT3Rs on emotion, systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety, which deeply hinders the current clinical application of 5-HT3R drugs. Therefore, the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.
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