Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions  

作　　者：Yinan DU Zhiwei LI Yukui ZHAO Jing HAN Weiping HU Zhiqiang LIU 

机构地区：[1]MOE Key Laboratory of Modern Teaching Technology,Shaanxi Normal University,Xi’an,710062,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2024年第1期23-37,共15页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Natural Science Foundation of China(Nos.82071516,32171065,91949105,and 81771227);the Innovation Capability Support Program of Shannxi Province in China(No.2020TD-037);the Fundamental Research Funds for the Central Universities(Nos.GK202105001,GK202205019,and CK202205022),China.

摘　　要：5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT_(3)R)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-HT_(3)R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT_(3)Rs 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-HT_(3)Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and theγ-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-HT_(3)R-induced GABA“disinhibition”mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT_(2)R-mediated regulation of anxiety reactions are also activated by 5-HT_(3)R-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-HT_(3)Rs.However,given the circuit specific modulation of 5-HT_(3)Rs on emotion,systemic use of 5-HT_(3)R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT_(3)R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

关 键 词：5-Hydroxytryptamine type 3 receptor(5-HT_(3)R) ANXIETY Medial prefrontal cortex AMYGDALA HIPPOCAMPUS Periaqueductal gray 

分 类 号：R969[医药卫生—药理学]