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

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

doi:10.1631/jzus.B2200642

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Review | Updated：2023-12-27

Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions
Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions
5-羟色胺3受体对焦虑反应的调节作用
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 1, Pages: 23-37(2024)
Affiliations：

MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi’an 710062, China
Funds：
DOI：10.1631/jzus.B2200642
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CSTR：

杜宜楠,李志伟,赵昱魁等.5-羟色胺3受体对焦虑反应的调节作用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(01):23-37.

Yinan DU, Zhiwei LI, Yukui ZHAO, et al. Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(1):23-37(2024)
杜宜楠,李志伟,赵昱魁等.5-羟色胺3受体对焦虑反应的调节作用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(01):23-37. DOI： 10.1631/jzus.B2200642.

Yinan DU, Zhiwei LI, Yukui ZHAO, et al. Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(1):23-37(2024) DOI： 10.1631/jzus.B2200642.

摘要

5-羟色胺3受体（5-hydroxytryptamine type 3 receptor，5-HT,3,R）是5-羟色胺受体家族中唯一的一类配体门控离子通道，通过对Na,+,、K,+,、Ca,2+,等离子的高通透性以及继发性电压门控Ca,2+,离子通道的激活从而诱发神经元兴奋性的快速上调或轴突末梢的神经递质释放。在中枢神经系统，5-HT,3,R广泛表达于内侧前额叶皮质、杏仁核、海马体和导水管周围灰质等与焦虑反应密切相关的脑区，通过对不同脑区不同类别细胞的作用，对焦虑反应产生双向调节效应。其中，5-HT,3,R在杏仁核通过激活胆囊收缩素系统促进焦虑；在内侧前额叶皮质的边缘下区通过激活γ-氨基丁酸能中间抑制性神经元的“去抑制”促进焦虑；在内侧前额叶皮质的边缘前区和腹侧海马则通过对γ-氨基丁酸能中间抑制性神经元的激活产生抗焦虑样作用。此外，在海马和导水管周围灰质，5-HT,3,R通过调节5-HT投射活动间接启动5-HT,2,R，从而参与焦虑反应调节。以上说明，仅通过全身性的激动或拮抗5-HT,3,R不太可能用于焦虑症治疗，这制约了当前5-HT,3,R药物的临床应用。因此，未来的研究可以探索针对5-HT,3,R涉及的环路进行靶向用药或联合药物的策略，以促进5-HT,3,R药物的临床应用。

Abstract

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 Ca,2+, 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 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-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-羟色胺3受体（5-HT3R）焦虑内侧前额叶皮质杏仁核海马体导水管周围灰质

Keywords

5-Hydroxytryptamine type 3 receptor (5-HT3R)AnxietyMedial prefrontal cortexAmygdalaHippocampusPeriaqueductal gray

references

Abela AR, Browne CJ, Sargin D, et al., 2020. Median raphe serotonin neurons promote anxiety-like behavior via inputs to the dorsal hippocampus. Neuropharmacology, 168:107985. https://doi.org/10.1016/j.neuropharm.2020.107985https://doi.org/10.1016/j.neuropharm.2020.107985

al Kury LT, Mahgoub M, Howarth FC, et al., 2018. Natural negative allosteric modulators of 5-HT3 receptors. Molecules, 23(12):3186. https://doi.org/10.3390/molecules23123186https://doi.org/10.3390/molecules23123186

Alves SH, Pinheiro G, Motta V, et al., 2004. Anxiogenic effects in the rat elevated plus-maze of 5-HT2C agonists into ventral but not dorsal hippocampus. Behav Pharmacol, 15(1):37-43. https://doi.org/10.1097/00008877-200402000-00005https://doi.org/10.1097/00008877-200402000-00005

Andrade TGCS, Macedo CEA, Zangrossi H, et al., 2004. Anxiolytic-like effects of median raphe nucleus lesion in the elevated T-maze. Behav Brain Res, 153(1):55-60. https://doi.org/10.1016/j.bbr.2003.10.036https://doi.org/10.1016/j.bbr.2003.10.036

Artaiz I, Romero G, Zazpe A, et al., 1995. The pharmacology of VA21B7: an atypical 5-HT3 receptor antagonist with anxiolytic-like properties in animal models. Psychopharmacology, 117(2):137-148. https://doi.org/10.1007/bf02245179https://doi.org/10.1007/bf02245179

Askari N, Moin M, Sanati M, et al., 2012. Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. CNS Drugs, 26(10):883-892. https://doi.org/10.2165/11635850-000000000-00000https://doi.org/10.2165/11635850-000000000-00000

Babaev O, Piletti Chatain C, Krueger-Burg D, 2018. Inhibition in the amygdala anxiety circuitry. Exp Mol Med, 50(4):1-16. https://doi.org/10.1038/s12276-018-0063-8https://doi.org/10.1038/s12276-018-0063-8

Bannerman DM, Matthews P, Deacon RM, et al., 2004. Medial septal lesions mimic effects of both selective dorsal and ventral hippocampal lesions. Behav Neurosci, 118(5):1033-1041. https://doi.org/10.1037/0735-7044.118.5.1033https://doi.org/10.1037/0735-7044.118.5.1033

Barnes JM, Barnes NM, Costall B, et al., 1990. Identification and distribution of 5-HT3 recognition sites within the human brainstem. Neurosci Lett, 111(1-2):80-86. https://doi.org/10.1016/0304-3940(90)90348-dhttps://doi.org/10.1016/0304-3940(90)90348-d

Barnes NM, Hales TG, Lummis SCR, et al., 2009. The 5-HT3 receptor ‍– the relationship between structure and function. Neuropharmacology, 56(1):273-284. https://doi.org/10.1016/j.neuropharm.2008.08.003https://doi.org/10.1016/j.neuropharm.2008.08.003

Basak S, Gicheru Y, Samanta A, et al., 2018. Cryo-EM structure of 5-HT3A receptor in its resting conformation. Nat Commun, 9:514. https://doi.org/10.1038/s41467-018-02997-4https://doi.org/10.1038/s41467-018-02997-4

Bhatnagar S, Nowak N, Babich L, et al., 2004. Deletion of the 5-HT3 receptor differentially affects behavior of males and females in the Porsolt forced swim and defensive withdrawal tests. Behav Brain Res, 153(2):527-535. https://doi.org/10.1016/j.bbr.2004.01.018https://doi.org/10.1016/j.bbr.2004.01.018

Bhatt S, Mahesh R, Devadoss T, et al., 2013. Anxiolytic-like effect of (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl)methanone (6g) in experimental mouse models of anxiety. Indian J Pharmacol, 45(3):248-251. https://doi.org/10.4103/0253-7613.111923https://doi.org/10.4103/0253-7613.111923

Bhatt S, Mahesh R, Jindal A, et al., 2017a. Neuropharmacological and neurochemical evaluation of N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n): a novel serotonergic 5-HT3 receptor antagonist for co-morbid antidepressant- and anxiolytic-like potential using traumatic brain injury model in rats. J Basic Clin Physiol Pharmacol, 28(2):93-100. https://doi.org/10.1515/jbcpp-2016-0057https://doi.org/10.1515/jbcpp-2016-0057

Bhatt S, Mahesh R, Devadoss T, et al., 2017b. Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice. J Basic Clin Physiol Pharmacol, 28(2):101-106. https://doi.org/10.1515/jbcpp-2016-0083https://doi.org/10.1515/jbcpp-2016-0083

Bhatt S, Devadoss T, Manjula SN, et al., 2021. 5-HT3 receptor antagonism: a potential therapeutic approach for the treatment of depression and other disorders. Curr Neuropharmacol, 19(9):1545-1559. https://doi.org/10.2174/1570159x18666201015155816https://doi.org/10.2174/1570159x18666201015155816

Bi WK, Luan SS, Wang J, et al., 2020. FSH signaling is involved in affective disorders. Biochem Biophys Res Commun, 525(4):915-920. https://doi.org/10.1016/j.bbrc.2020.03.039https://doi.org/10.1016/j.bbrc.2020.03.039

Birbaumer N, Grodd W, Diedrich O, et al., 1998. fMRI reveals amygdala activation to human faces in social phobics. NeuroReport, 9(6):1223-1226. https://doi.org/10.1097/00001756-199804200-00048https://doi.org/10.1097/00001756-199804200-00048

Bremner JD, Randall P, Scott TM, et al., 1995. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry, 152(7):973-981. https://doi.org/10.1176/ajp.152.7.973https://doi.org/10.1176/ajp.152.7.973

Bremner JD, Hoffman M, Afzal N, et al., 2021. The environment contributes more than genetics to smaller hippocampal volume in Posttraumatic Stress Disorder (PTSD). J Psychiatr Res, 137:579-588. https://doi.org/10.1016/j.jpsychires.2020.10.042https://doi.org/10.1016/j.jpsychires.2020.10.042

Campbell AD, Womer DE, Simon JR, 1995. The 5-HT3 receptor agonist 1-‍(m-chlorophenyl)‍-biguanide interacts with the dopamine transporter in rat brain synaptosomes. Eur J Pharmacol: Mol Pharmacol, 290(2):157-162. https://doi.org/10.1016/0922-4106(95)90029-2https://doi.org/10.1016/0922-4106(95)90029-2

Celli J, Rappold G, Niesler B, 2017. The human serotonin type 3 receptor gene (HTR3A-E) allelic variant database. Hum Mutat, 38(2):137-147. https://doi.org/10.1002/humu.23136https://doi.org/10.1002/humu.23136

Challis C, Beck SG, Berton O, 2014. Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective choices after social defeat. Front Behav Neurosci, 8:43. https://doi.org/10.3389/fnbeh.2014.00043https://doi.org/10.3389/fnbeh.2014.00043

Choi IS, Cho JH, Kim JT, et al., 2007. Serotoninergic modulation of GABAergic synaptic transmission in developing rat CA3 pyramidal neurons. J Neurochem, 103(6):‍2342-2353. https://doi.org/10.1111/j.1471-4159.2007.04945.xhttps://doi.org/10.1111/j.1471-4159.2007.04945.x

Cortes-Altamirano JL, Olmos-Hernandez A, Jaime HB, et al., 2018. Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 receptors and their role in the modulation of pain response in the central nervous system. Curr Neuropharmacol, 16(2):210-221. https://doi.org/10.2174/1570159x15666170911121027https://doi.org/10.2174/1570159x15666170911121027

Costall B, Kelly ME, Naylor RJ, et al., 1989. Neuroanatomical sites of action of 5-HT3 receptor agonist and antagonists for alteration of aversive behaviour in the mouse. Br J Pharmacol, 96(2):325-332. https://doi.org/10.1111/j.1476-5381.1989.tb11821.xhttps://doi.org/10.1111/j.1476-5381.1989.tb11821.x

Crocq MA, 2015. A history of anxiety: from hippocrates to DSM. Dialogues Clin Neurosci, 17(3):319-325. https://doi.org/10.31887/DCNS.2015.17.3/macrocqhttps://doi.org/10.31887/DCNS.2015.17.3/macrocq

Cutler MG, 1991. An ethological study of the effects of buspirone and the 5-HT3 receptor antagonist, BRL 43694 (granisetron) on behaviour during social interactions in female and male mice. Neuropharmacology, 30(4):299-306. https://doi.org/10.1016/0028-3908(91)90053-ehttps://doi.org/10.1016/0028-3908(91)90053-e

de la Mora MP, Hernández-Gómez AM, Arizmendi-García Y, et al., 2007. Role of the amygdaloid cholecystokinin (CCK)/gastrin-2 receptors and terminal networks in the modulation of anxiety in the rat. Effects of CCK-4 and CCK-8S on anxiety-like behaviour and [3H]GABA release. Eur J Neurosci, 26(12):3614-3630. https://doi.org/10.1111/j.1460-9568.2007.05963.xhttps://doi.org/10.1111/j.1460-9568.2007.05963.x

del Boca C, Lutz PE, le Merrer J, et al., 2012. Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice. Neuroscience, 218:185-195. https://doi.org/10.1016/j.neuroscience.2012.05.022https://doi.org/10.1016/j.neuroscience.2012.05.022

el Nebrisi E, Prytkova T, Lorke DE, et al., 2020. Capsaicin is a negative allosteric modulator of the 5-HT3 receptor. Front Pharmacol, 11:1274. https://doi.org/10.3389/fphar.2020.01274https://doi.org/10.3389/fphar.2020.01274

Engin E, Treit D, 2007. The role of hippocampus in anxiety: intracerebral infusion studies. Behav Pharmacol, 18(5-6):365-374. https://doi.org/10.1097/FBP.0b013e3282de7929https://doi.org/10.1097/FBP.0b013e3282de7929

Fawley JA, Doyle MW, Andresen MC, 2019. 5-HT3R-sourced calcium enhances glutamate release from a distinct vesicle pool. Brain Res, 1721:146346. https://doi.org/10.1016/j.brainres.2019.146346https://doi.org/10.1016/j.brainres.2019.146346

Gasiorek A, Trattnig SM, Ahring PK, et al., 2016. Delineation of the functional properties and the mechanism of action of TMPPAA, an allosteric agonist and positive allosteric modulator of 5-HT3 receptors. Biochem Pharmacol, 110-111:92-108. https://doi.org/10.1016/j.bcp.2016.04.004https://doi.org/10.1016/j.bcp.2016.04.004

Giacobbe P, Flint A, 2018. Diagnosis and management of anxiety disorders. Continuum (Minneap Minn), 24(3):893-919. https://doi.org/10.1212/con.0000000000000607https://doi.org/10.1212/con.0000000000000607

Gibbs E, Chakrapani S, 2021. Structure, function and physiology of 5-hydroxytryptamine receptors subtype 3. In: Harris JR, Marles-Wright J (Eds.), Macromolecular Protein Complexes III: Structure and Function. Springer, Cham, p.373-408. https://doi.org/10.1007/978-3-030-58971-4_11https://doi.org/10.1007/978-3-030-58971-4_11

Giordano J, Gerstmann H, 2004. Patterns of serotonin- and 2-methylserotonin-induced pain may reflect 5-HT3 receptor sensitization. Eur J Pharmacol, 483(2-3):267-269. https://doi.org/10.1016/j.ejphar.2003.10.044https://doi.org/10.1016/j.ejphar.2003.10.044

Griffiths JL, Lovick TA, 2002. Co-localization of 5-HT2A-receptor- and GABA-immunoreactivity in neurones in the periaqueductal grey matter of the rat. Neurosci Lett, 326(3):151-154. https://doi.org/10.1016/s0304-3940(02)00182-9https://doi.org/10.1016/s0304-3940(02)00182-9

Gui ZH, Zhang QJ, Liu J, et al., 2010. In vivo modulation of the firing activity of putative slow- and fast-spiking interneurons in the medial prefrontal cortex by 5-HT3 receptors in 6-hydroxydopamine-induced Parkinsonian rats. Neuroscience, 169(3):1315-1325. https://doi.org/10.1016/j.neuroscience.2010.05.059https://doi.org/10.1016/j.neuroscience.2010.05.059

Gupta D, Thangaraj D, Radhakrishnan M, 2016. A novel 5HT3 antagonist 4i (N-(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide) prevents diabetes-induced depressive phenotypes in mice: modulation of serotonergic system. Behav Brain Res, 297:41-50. https://doi.org/10.1016/j.bbr.2015.10.007https://doi.org/10.1016/j.bbr.2015.10.007

Harmer CJ, Reid CB, Ray MK, et al., 2006. 5HT3 antagonism abolishes the emotion potentiated startle effect in humans. Psychopharmacology, 186:18-24. https://doi.org/10.1007/s00213-006-0337-zhttps://doi.org/10.1007/s00213-006-0337-z

Harrell AV, Allan AM, 2003. Improvements in hippocampal-dependent learning and decremental attention in 5-HT3 receptor overexpressing mice. Learn Mem, 10(5):410-419. https://doi.org/10.1101/lm.56103https://doi.org/10.1101/lm.56103

Haus U, Varga B, Stratz T, et al., 2000. Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain. Scand J Rheumatol, 29(113):55-58. https://doi.org/10.1080/030097400446652https://doi.org/10.1080/030097400446652

Hensler JG, Hodge CW, Overstreet DH, 2004. Reduced 5-HT3 receptor binding and lower baseline plus maze anxiety in the alcohol-preferring inbred fawn-hooded rat. Pharmacol Biochem Behav, 77(2):281-289. https://doi.org/10.1016/j.pbb.2003.11.015https://doi.org/10.1016/j.pbb.2003.11.015

Hewlett WA, Schmid SP, Salomon RM, 2003. Pilot trial of ondansetron in the treatment of 8 patients with obsessive-compulsive disorder. J Clin Psychiatry, 64(9):1025-1030. https://doi.org/10.4088/jcp.v64n0907https://doi.org/10.4088/jcp.v64n0907

Higgins GA, Jones BJ, Oakley NR, et al., 1991. Evidence that the amygdala is involved in the disinhibitory effects of 5-HT3 receptor antagonists. Psychopharmacology, 104(4):545-551. https://doi.org/10.1007/bf02245664https://doi.org/10.1007/bf02245664

Holm L, Liang W, Thorsell A, et al., 2014. Acute effects on brain cholecystokinin-like concentration and anxiety-like behaviour in the female rat upon a single injection of 17β‍-estradiol. Pharmacol Biochem Behav, 122:222-227. https://doi.org/10.1016/j.pbb.2014.04.004https://doi.org/10.1016/j.pbb.2014.04.004

Hutchison SM, Mâsse LC, Pawluski JL, et al., 2021. Perinatal selective serotonin reuptake inhibitor (SSRI) and other antidepressant exposure effects on anxiety and depressive behaviors in offspring: a review of findings in humans and rodent models. Reprod Toxicol, 99:80-95. https://doi.org/10.1016/j.reprotox.2020.11.013https://doi.org/10.1016/j.reprotox.2020.11.013

Irving H, Turek I, Kettle C, et al., 2021. Tapping into 5-HT3 receptors to modify metabolic and immune responses. Int J Mol Sci, 22(21):11910. https://doi.org/10.3390/ijms222111910https://doi.org/10.3390/ijms222111910

Juza R, Vlcek P, Mezeiova E, et al., 2020. Recent advances with 5-HT3 modulators for neuropsychiatric and gastrointestinal disorders. Med Res Rev, 40(5):1593-1678. https://doi.org/10.1002/med.21666https://doi.org/10.1002/med.21666

Kilpatrick GJ, Jones BJ, Tyers MB, 1987. Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature, 330(6150):746-748. https://doi.org/10.1038/330746a0https://doi.org/10.1038/330746a0

Kilpatrick GJ, Butler A, Burridge J, et al., 1990. 1-‍(m-Chlorophenyl)‍-biguanide, a potent high affinity 5-HT3 receptor agonist. Eur J Pharmacol, 182(1):193-197. https://doi.org/10.1016/0014-2999(90)90513-6https://doi.org/10.1016/0014-2999(90)90513-6

Koch SBJ, van Zuiden M, Nawijn L, et al., 2017. Decreased uncinate fasciculus tract integrity in male and female patients with PTSD: a diffusion tensor imaging study. J Psychiatry Neurosci, 42(5):331-342. https://doi.org/10.1503/jpn.160129https://doi.org/10.1503/jpn.160129

Koyama Y, Kondo M, Shimada S, 2017. Building a 5-HT3A receptor expression map in the mouse brain. Sci Rep, 7:42884. https://doi.org/10.1038/srep42884https://doi.org/10.1038/srep42884

Kurhe Y, Mahesh R, Devadoss T, 2015. QCM-4, a 5-HT3 receptor antagonist ameliorates plasma HPA axis hyperactivity, leptin resistance and brain oxidative stress in depression and anxiety-like behavior in obese mice. Biochem Biophys Res Commun, 456(1):74-79. https://doi.org/10.1016/j.bbrc.2014.11.036https://doi.org/10.1016/j.bbrc.2014.11.036

Kurhe Y, Mahesh R, Devadoss T, 2017. Novel 5-HT3 receptor antagonist QCM-4 attenuates depressive-like phenotype associated with obesity in high-fat-diet-fed mice. Psychopharmacology, 234(7):1165-1179. https://doi.org/10.1007/s00213-017-4558-0https://doi.org/10.1007/s00213-017-4558-0

Lakhtakia T, Torous J, 2022. Current directions in digital interventions for mood and anxiety disorders. Curr Opin Psychiatry, 35(2):130-135. https://doi.org/10.1097/yco.0000000000000772https://doi.org/10.1097/yco.0000000000000772

Lecrubier Y, Puech AJ, Azcona A, et al., 1993. A randomized double-blind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder. Psychopharmacology, 112:129-133. https://doi.org/10.1007/bf02247373https://doi.org/10.1007/bf02247373

Li HH, Liu YT, Gao XQ, et al., 2019. Neuroplastin 65 modulates anxiety- and depression-like behavior likely through adult hippocampal neurogenesis and central 5-HT activity. FEBS J, 286(17):3401-3415. https://doi.org/10.1111/febs.14865https://doi.org/10.1111/febs.14865

Lopes LT, Canto-de-Souza L, Baptista-de-Souza D, et al., 2022. The interplay between 5-HT2C and 5-HT3A receptors in the dorsal periaqueductal gray mediates anxiety-like behavior in mice. Behav Brain Res, 417:113588. https://doi.org/10.1016/j.bbr.2021.113588https://doi.org/10.1016/j.bbr.2021.113588

Lummis SCR, 2012. 5-HT3 receptors. J Biol Chem, 287(48):40239-40245. https://doi.org/10.1074/jbc.R112.406496https://doi.org/10.1074/jbc.R112.406496

Machu TK, 2011. Therapeutics of 5-HT3 receptor antagonists: current uses and future directions. Pharmacol Ther, 130(3):338-347. https://doi.org/10.1016/j.pharmthera.2011.02.003https://doi.org/10.1016/j.pharmthera.2011.02.003

Maksay G, Bíró T, Bugovics G, 2005. Allosteric modulation of 5-HT3 serotonin receptors. Eur J Pharmacol, 514(1):17-24. https://doi.org/10.1016/j.ejphar.2005.03.019https://doi.org/10.1016/j.ejphar.2005.03.019

Marcinkiewcz CA, Mazzone CM, D'Agostino G, et al., 2016. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature, 537(7618):97-101. https://doi.org/10.1038/nature19318https://doi.org/10.1038/nature19318

Martin KF, Hannon S, Phillips I, et al., 1992. Opposing roles for 5-HT1B and 5-HT3 receptors in the control of 5-HT release in rat hippocampus in vivo. Br J Pharmacol, 106(1):139-142. https://doi.org/10.1111/j.1476-5381.1992.tb14306.xhttps://doi.org/10.1111/j.1476-5381.1992.tb14306.x

Mascagni F, McDonald AJ, 2007. A novel subpopulation of 5-HT type 3A receptor subunit immunoreactive interneurons in the rat basolateral amygdala. Neuroscience, 144(3):1015-1024. https://doi.org/10.1016/j.neuroscience.2006.10.044https://doi.org/10.1016/j.neuroscience.2006.10.044

McCann UD, Morgan CM, Geraci M, et al., 1997. Effects of the 5-HT3 antagonist, ondansetron, on the behavioral and physiological effects of pentagastrin in patients with panic disorder and social phobia. Neuropsychopharmacology, 17(6):360-369. https://doi.org/10.1016/s0893-133x(97)00085-7https://doi.org/10.1016/s0893-133x(97)00085-7

Mendelson SD, McEwen BS, 1991. Autoradiographic analyses of the effects of restraint-induced stress on 5-HT1A, 5-HT1C and 5-HT2 receptors in the dorsal hippocampus of male and female rats. Neuroendocrinology, 54(5):454-461. https://doi.org/10.1159/000125951https://doi.org/10.1159/000125951

Millan MJ, 2022. Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action. Ther Adv Psychopharmacol, 12:20451253221105128. https://doi.org/10.1177/20451253221105128https://doi.org/10.1177/20451253221105128

Motzkin JC, Philippi CL, Wolf RC, et al., 2015. Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans. Biol Psychiatry, 77(3):276-284. https://doi.org/10.1016/j.biopsych.2014.02.014https://doi.org/10.1016/j.biopsych.2014.02.014

Murphy SE, Capitão LP, Giles SLC, et al., 2021. The knowns and unknowns of SSRI treatment in young people with depression and anxiety: efficacy, predictors, and mechanisms of action. Lancet Psychiatry, 8(9):824-835. https://doi.org/10.1016/s2215-0366(21)00154-1https://doi.org/10.1016/s2215-0366(21)00154-1

Nowicki M, Tran S, Muraleetharan A, et al., 2014. Serotonin antagonists induce anxiolytic and anxiogenic-like behavior in zebrafish in a receptor-subtype dependent manner. Pharmacol Biochem Behav, 126:170-180. https://doi.org/10.1016/j.pbb.2014.09.022https://doi.org/10.1016/j.pbb.2014.09.022

Pallanti S, Bernardi S, Antonini S, et al., 2009. Ondansetron augmentation in treatment-resistant obsessive-compulsive disorder: a preliminary, single-blind, prospective study. CNS Drugs, 23(12):1047-1055. https://doi.org/10.2165/11530240-000000000-00000https://doi.org/10.2165/11530240-000000000-00000

Park J, Moghaddam B, 2017. Impact of anxiety on prefrontal cortex encoding of cognitive flexibility. Neuroscience, 345:193-202. https://doi.org/10.1016/j.neuroscience.2016.06.013https://doi.org/10.1016/j.neuroscience.2016.06.013

Riga MS, Sánchez C, Celada P, et al., 2016. Involvement of 5-HT3 receptors in the action of vortioxetine in rat brain: focus on glutamatergic and GABAergic neurotransmission. Neuropharmacology, 108:73-81. https://doi.org/10.1016/j.neuropharm.2016.04.023https://doi.org/10.1016/j.neuropharm.2016.04.023

Rogan MT, Stäubli UV, Ledoux JE, 1997. Fear conditioning induces associative long-term potentiation in the amygdala. Nature, 390(6660):604-607. https://doi.org/10.1038/37601https://doi.org/10.1038/37601

Sah P, 2017. Fear, anxiety, and the amygdala. Neuron, 96(1):1-2. https://doi.org/10.1016/j.neuron.2017.09.013https://doi.org/10.1016/j.neuron.2017.09.013

Serata D, Kotzalidis GD, Rapinesi C, et al., 2015. Are 5-HT3 antagonists effective in obsessive-compulsive disorder? A systematic review of literature. Hum Psychopharmacol, 30(2):70-84. https://doi.org/10.1002/hup.2461https://doi.org/10.1002/hup.2461

Sharafkhah M, Alamdar MA, Massoudifar A, et al., 2019. Comparing the efficacy of ondansetron and granisetron augmentation in treatment-resistant obsessive-compulsive disorder: a randomized double-blind placebo-controlled study. Int Clin Psychopharmacol, 34(5):222-233. https://doi.org/10.1097/yic.0000000000000267https://doi.org/10.1097/yic.0000000000000267

Sharp T, Barnes NM, 2020. Central 5-HT receptors and their function; present and future. Neuropharmacology, 177:108155. https://doi.org/10.1016/j.neuropharm.2020.108155https://doi.org/10.1016/j.neuropharm.2020.108155

Ślifirski G, Król M, Turło J, 2021. 5-HT receptors and the development of new antidepressants. Int J Mol Sci, 22(16):9015. https://doi.org/10.3390/ijms22169015https://doi.org/10.3390/ijms22169015

Smith WT, Londborg PD, Blomgren SL, et al., 1999. Pilot study of zatosetron (LY277359) maleate, a 5-hydroxytryptamine-3 antagonist, in the treatment of anxiety. J Clin Psychopharmacol, 19(2):125-131. https://doi.org/10.1097/00004714-199904000-00006https://doi.org/10.1097/00004714-199904000-00006

Solt K, Ruesch D, Forman SA, et al., 2007. Differential effects of serotonin and dopamine on human 5-HT3A receptor kinetics: interpretation within an allosteric kinetic model. J Neurosci, 27(48):13151-13160. https://doi.org/10.1523/jneurosci.3772-07.2007https://doi.org/10.1523/jneurosci.3772-07.2007

Soltani F, Sayyah M, Feizy F, et al., 2010. A double-blind, placebo-controlled pilot study of ondansetron for patients with obsessive-compulsive disorder. Hum Psychopharmacol, 25(6):509-513. https://doi.org/10.1002/hup.1145https://doi.org/10.1002/hup.1145

Stefański R, Pałejko W, Bidzinski A, et al., 1993. Serotonergic innervation of the hippocampus and nucleus accumbens septi and the anxiolytic-like action of the 5-HT3 receptor antagonists. Neuropharmacology, 32(10):‍987-993. https://doi.org/10.1016/0028-3908(93)90063-9https://doi.org/10.1016/0028-3908(93)90063-9

Szeszko PR, Robinson D, Alvir JMJ, et al., 1999. Orbital frontal and amygdala volume reductions in obsessive-compulsive disorder. Arch Gen Psychiatry, 56(10):913-919. https://doi.org/10.1001/archpsyc.56.10.913https://doi.org/10.1001/archpsyc.56.10.913

Taylor NE, Pei JZ, Zhang J, et al., 2019. The role of glutamatergic and dopaminergic neurons in the periaqueductal gray/dorsal raphe: separating analgesia and anxiety. eNeuro, 6(1):ENEURO.0018-18.2019. https://doi.org/10.1523/eneuro.0018-18.2019https://doi.org/10.1523/eneuro.0018-18.2019

Togao O, Yoshiura T, Nakao T, et al., 2010. Regional gray and white matter volume abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study. Psychiatry Res Neuroimaging, 184(1):29-37. https://doi.org/10.1016/j.pscychresns.2010.06.011https://doi.org/10.1016/j.pscychresns.2010.06.011

Tovote P, Fadok JP, Lüthi A, 2015. Neuronal circuits for fear and anxiety. Nat Rev Neurosci, 16(6):317-331. https://doi.org/10.1038/nrn3945https://doi.org/10.1038/nrn3945

Tovote P, Esposito MS, Botta P, et al., 2016. Midbrain circuits for defensive behaviour. Nature, 534(7606):206-212. https://doi.org/10.1038/nature17996https://doi.org/10.1038/nature17996

Tseilikman V, Akulov A, Shevelev O, et al., 2022. Paradoxical anxiety level reduction in animal chronic stress: a unique role of hippocampus neurobiology. Int J Mol Sci, 23(16):9151. https://doi.org/10.3390/ijms23169151https://doi.org/10.3390/ijms23169151

Turner TJ, Mokler DJ, Luebke JI, 2004. Calcium influx through presynaptic 5-HT3 receptors facilitates GABA release in the hippocampus: in vitro slice and synaptosome studies. Neuroscience, 129(3):703-718. https://doi.org/10.1016/j.neuroscience.2004.08.020https://doi.org/10.1016/j.neuroscience.2004.08.020

Urzedo-Rodrigues LS, Ferreira HS, Santana RC, et al., 2014. Blockade of 5-HT3 receptors in the septal area increases Fos expression in selected brain areas. Auton Neurosci, 181:55-68. https://doi.org/10.1016/j.autneu.2014.01.003https://doi.org/10.1016/j.autneu.2014.01.003

Uvnäs-Moberg K, Hillegaart V, Alster P, et al., 1996. Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin, CCK, gastrin and somatostatin plasma levels in the rat. Neuropharmacology, 35(11):1635-1640. https://doi.org/10.1016/s0028-3908(96)00078-0https://doi.org/10.1016/s0028-3908(96)00078-0

Vilela-Costa HH, Maraschin JC, Casarotto PC, et al., 2021. Role of 5-HT1A and 5-HT2C receptors of the dorsal periaqueductal gray in the anxiety- and panic-modulating effects of antidepressants in rats. Behav Brain Res, 404:113159. https://doi.org/10.1016/j.bbr.2021.113159https://doi.org/10.1016/j.bbr.2021.113159

Vu V, Conant-Norville D, 2021. Anxiety: recognition and treatment options. Psychiatr Clin North Am, 44(3):373-380. https://doi.org/10.1016/j.psc.2021.04.005https://doi.org/10.1016/j.psc.2021.04.005

Yakel JL, Jackson MB, 1988. 5-HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell line. Neuron, 1(7):615-621. https://doi.org/10.1016/0896-6273(88)90111-0https://doi.org/10.1016/0896-6273(88)90111-0

Yakel JL, Shao XM, Jackson MB, 1990. The selectivity of the channel coupled to the 5-HT3 receptor. Brain Res, 533(1):46-52. https://doi.org/10.1016/0006-8993(90)91793-ghttps://doi.org/10.1016/0006-8993(90)91793-g

Zhao HY, Lin Y, Chen SR, et al., 2018. 5-HT3 receptors: a potential therapeutic target for epilepsy. Curr Neuropharmacol, 16(1):29-36. https://doi.org/10.2174/1570159x15666170508170412https://doi.org/10.2174/1570159x15666170508170412

Zwanzger P, Domschke K, Bradwejn J, 2012. Neuronal network of panic disorder: the role of the neuropeptide cholecystokinin. Depress Anxiety, 29(9):762-774. https://doi.org/10.1002/da.21919https://doi.org/10.1002/da.21919

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