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 Yinan DU;Zhiwei LI;Yukui ZHAO;Jing HAN;Weiping HU;Zhiqiang LIU

作者机构：MOE Key Laboratory of Modern Teaching TechnologyShaanxi Normal UniversityXi’an710062China 

出 版 物：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 (浙江大学学报（英文版）B辑（生物医学与生物技术）)

年 卷 期：2024年第25卷第1期

页      面：23-37页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1001[医学-基础医学(可授医学、理学学位)] 0836[工学-生物工程] 100602[医学-中西医结合临床] 10[医学] 

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 

主　　题：5-Hydroxytryptamine type 3 receptor(5-HT_(3)R) Anxiety Medial prefrontal cortex Amygdala Hippocampus Periaqueductal gray 

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 *** 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 *** 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)“disinhibitionmechanism 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“disinhibitionmechanism 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 *** provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT_(3)***,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 ***,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.