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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.1 P.23-37


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

Author(s):  Yinan DU, Zhiwei LI, Yukui ZHAO, Jing HAN, Weiping HU, Zhiqiang LIU

Affiliation(s):  MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xian 710062, China

Corresponding email(s):   liuzhiqiang@snnu.edu.cn, weipinghu@163.com

Key Words:  5-Hydroxytryptamine type 3 receptor (5-HT3R), Anxiety, Medial prefrontal cortex, Amygdala, Hippocampus, Periaqueductal gray

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.

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journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

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%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
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%P 23-37
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%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200642

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
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%@ 1673-1581
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2200642

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.


摘要:5-羟色胺3受体(5-hydroxytryptamine type 3 receptor,5-HT3R)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+、Ca2+等离子的高通透性以及继发性电压门控Ca2+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-HT3R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-HT3R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-HT3R通过调节5-HT投射活动间接启动5-HT2R,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-HT3R不太可能用于焦虑症治疗,这制约了当前5-HT3R药物的临床应用。因此,未来的研究可以探索针对5-HT3R涉及的环路进行靶向用药或联合药物的策略,以促进5-HT3R药物的临床应用。


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[1]AbelaAR, BrowneCJ, SarginD, et al., 2020. Median raphe serotonin neurons promote anxiety-like behavior via inputs to the dorsal hippocampus. Neuropharmacology, 168:107985.

[2]al KuryLT, MahgoubM, HowarthFC, et al., 2018. Natural negative allosteric modulators of 5-HT3 receptors. Molecules, 23(12):3186.

[3]AlvesSH, PinheiroG, MottaV, 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.

[4]AndradeTGCS, MacedoCEA, ZangrossiH, et al., 2004. Anxiolytic-like effects of median raphe nucleus lesion in the elevated T-maze. Behav Brain Res, 153(1):55-60.

[5]ArtaizI, RomeroG, ZazpeA, 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.

[6]AskariN, MoinM, SanatiM, 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.

[7]BabaevO, Piletti ChatainC, Krueger-BurgD, 2018. Inhibition in the amygdala anxiety circuitry. Exp Mol Med, 50(4):1-16.

[8]BannermanDM, MatthewsP, DeaconRM, et al., 2004. Medial septal lesions mimic effects of both selective dorsal and ventral hippocampal lesions. Behav Neurosci, 118(5):1033-1041.

[9]BarnesJM, BarnesNM, CostallB, et al., 1990. Identification and distribution of 5-HT3 recognition sites within the human brainstem. Neurosci Lett, 111(1-2):80-86.

[10]BarnesNM, HalesTG, LummisSCR, et al., 2009. The 5-HT3 receptor ‍– the relationship between structure and function. Neuropharmacology, 56(1):273-284.

[11]BasakS, GicheruY, SamantaA, et al., 2018. Cryo-EM structure of 5-HT3A receptor in its resting conformation. Nat Commun, 9:514.

[12]BhatnagarS, NowakN, BabichL, 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.

[13]BhattS, MaheshR, DevadossT, 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.

[14]BhattS, MaheshR, JindalA, 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.

[15]BhattS, MaheshR, DevadossT, 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.

[16]BhattS, DevadossT, ManjulaSN, 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.

[17]BiWK, LuanSS, WangJ, et al., 2020. FSH signaling is involved in affective disorders. Biochem Biophys Res Commun, 525(4):915-920.

[18]BirbaumerN, GroddW, DiedrichO, et al., 1998. fMRI reveals amygdala activation to human faces in social phobics. NeuroReport, 9(6):1223-1226.

[19]BremnerJD, RandallP, ScottTM, et al., 1995. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry, 152(7):973-981.

[20]BremnerJD, HoffmanM, AfzalN, et al., 2021. The environment contributes more than genetics to smaller hippocampal volume in Posttraumatic Stress Disorder (PTSD). J Psychiatr Res, 137:579-588.

[21]CampbellAD, WomerDE, SimonJR, 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.

[22]CelliJ, RappoldG, NieslerB, 2017. The human serotonin type 3 receptor gene (HTR3A-E) allelic variant database. Hum Mutat, 38(2):137-147.

[23]ChallisC, BeckSG, BertonO, 2014. Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective choices after social defeat. Front Behav Neurosci, 8:43.

[24]ChoiIS, ChoJH, KimJT, et al., 2007. Serotoninergic modulation of GABAergic synaptic transmission in developing rat CA3 pyramidal neurons. J Neurochem, 103(6):‍2342-2353.

[25]Cortes-AltamiranoJL, Olmos-HernandezA, JaimeHB, 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.

[26]CostallB, KellyME, NaylorRJ, 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.

[27]CrocqMA, 2015. A history of anxiety: from hippocrates to DSM. Dialogues Clin Neurosci, 17(3):319-325.

[28]CutlerMG, 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.

[29]de la MoraMP, Hernández-GómezAM, Arizmendi-GarcíaY, 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.

[30]del BocaC, LutzPE, le MerrerJ, et al., 2012. Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice. Neuroscience, 218:185-195.

[31]el NebrisiE, PrytkovaT, LorkeDE, et al., 2020. Capsaicin is a negative allosteric modulator of the 5-HT3 receptor. Front Pharmacol, 11:1274.

[32]EnginE, TreitD, 2007. The role of hippocampus in anxiety: intracerebral infusion studies. Behav Pharmacol, 18(5-6):365-374.

[33]FawleyJA, DoyleMW, AndresenMC, 2019. 5-HT3R-sourced calcium enhances glutamate release from a distinct vesicle pool. Brain Res, 1721:146346.

[34]GasiorekA, TrattnigSM, AhringPK, 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.

[35]GiacobbeP, FlintA, 2018. Diagnosis and management of anxiety disorders. Continuum (Minneap Minn), 24(3):893-919.

[36]GibbsE, ChakrapaniS, 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.

[37]GiordanoJ, GerstmannH, 2004. Patterns of serotonin- and 2-methylserotonin-induced pain may reflect 5-HT3 receptor sensitization. Eur J Pharmacol, 483(2-3):267-269.

[38]GriffithsJL, LovickTA, 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.

[39]GuiZH, ZhangQJ, LiuJ, 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.

[40]GuptaD, ThangarajD, RadhakrishnanM, 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.

[41]HarmerCJ, ReidCB, RayMK, et al., 2006. 5HT3 antagonism abolishes the emotion potentiated startle effect in humans. Psychopharmacology, 186:18-24.

[42]HarrellAV, AllanAM, 2003. Improvements in hippocampal-dependent learning and decremental attention in 5-HT3 receptor overexpressing mice. Learn Mem, 10(5):410-419.

[43]HausU, VargaB, StratzT, 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.

[44]HenslerJG, HodgeCW, OverstreetDH, 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.

[45]HewlettWA, SchmidSP, SalomonRM, 2003. Pilot trial of ondansetron in the treatment of 8 patients with obsessive-compulsive disorder. J Clin Psychiatry, 64(9):1025-1030.

[46]HigginsGA, JonesBJ, OakleyNR, et al., 1991. Evidence that the amygdala is involved in the disinhibitory effects of 5-HT3 receptor antagonists. Psychopharmacology, 104(4):545-551.

[47]HolmL, LiangW, ThorsellA, 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.

[48]HutchisonSM, MâsseLC, PawluskiJL, 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.

[49]IrvingH, TurekI, KettleC, et al., 2021. Tapping into 5-HT3 receptors to modify metabolic and immune responses. Int J Mol Sci, 22(21):11910.

[50]JuzaR, VlcekP, MezeiovaE, et al., 2020. Recent advances with 5-HT3 modulators for neuropsychiatric and gastrointestinal disorders. Med Res Rev, 40(5):1593-1678.

[51]KilpatrickGJ, JonesBJ, TyersMB, 1987. Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature, 330(6150):746-748.

[52]KilpatrickGJ, ButlerA, BurridgeJ, et al., 1990. 1-‍(m-Chlorophenyl)‍-biguanide, a potent high affinity 5-HT3 receptor agonist. Eur J Pharmacol, 182(1):193-197.

[53]KochSBJ, van ZuidenM, NawijnL, 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.

[54]KoyamaY, KondoM, ShimadaS, 2017. Building a 5-HT3A receptor expression map in the mouse brain. Sci Rep, 7:42884.

[55]KurheY, MaheshR, DevadossT, 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.

[56]KurheY, MaheshR, DevadossT, 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.

[57]LakhtakiaT, TorousJ, 2022. Current directions in digital interventions for mood and anxiety disorders. Curr Opin Psychiatry, 35(2):130-135.

[58]LecrubierY, PuechAJ, AzconaA, 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.

[59]LiHH, LiuYT, GaoXQ, 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.

[60]LopesLT, Canto-de-SouzaL, Baptista-de-SouzaD, 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.

[61]LummisSCR, 2012. 5-HT3 receptors. J Biol Chem, 287(48):40239-40245.

[62]MachuTK, 2011. Therapeutics of 5-HT3 receptor antagonists: current uses and future directions. Pharmacol Ther, 130(3):338-347.

[63]MaksayG, BíróT, BugovicsG, 2005. Allosteric modulation of 5-HT3 serotonin receptors. Eur J Pharmacol, 514(1):17-24.

[64]MarcinkiewczCA, MazzoneCM, D'AgostinoG, et al., 2016. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature, 537(7618):97-101.

[65]MartinKF, HannonS, PhillipsI, 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.

[66]MascagniF, McDonaldAJ, 2007. A novel subpopulation of 5-HT type 3A receptor subunit immunoreactive interneurons in the rat basolateral amygdala. Neuroscience, 144(3):1015-1024.

[67]McCannUD, MorganCM, GeraciM, 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.

[68]MendelsonSD, McEwenBS, 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.

[69]MillanMJ, 2022. Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action. Ther Adv Psychopharmacol, 12:20451253221105128.

[70]MotzkinJC, PhilippiCL, WolfRC, et al., 2015. Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans. Biol Psychiatry, 77(3):276-284.

[71]MurphySE, CapitãoLP, GilesSLC, 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.

[72]NowickiM, TranS, MuraleetharanA, 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.

[73]PallantiS, BernardiS, AntoniniS, et al., 2009. Ondansetron augmentation in treatment-resistant obsessive-compulsive disorder: a preliminary, single-blind, prospective study. CNS Drugs, 23(12):1047-1055.

[74]ParkJ, MoghaddamB, 2017. Impact of anxiety on prefrontal cortex encoding of cognitive flexibility. Neuroscience, 345:193-202.

[75]RigaMS, SánchezC, CeladaP, 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.

[76]RoganMT, StäubliUV, LedouxJE, 1997. Fear conditioning induces associative long-term potentiation in the amygdala. Nature, 390(6660):604-607.

[77]SahP, 2017. Fear, anxiety, and the amygdala. Neuron, 96(1):1-2.

[78]SerataD, KotzalidisGD, RapinesiC, et al., 2015. Are 5-HT3 antagonists effective in obsessive-compulsive disorder? A systematic review of literature. Hum Psychopharmacol, 30(2):70-84.

[79]SharafkhahM, AlamdarMA, MassoudifarA, 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.

[80]SharpT, BarnesNM, 2020. Central 5-HT receptors and their function; present and future. Neuropharmacology, 177:108155.

[81]ŚlifirskiG, KrólM, TurłoJ, 2021. 5-HT receptors and the development of new antidepressants. Int J Mol Sci, 22(16):9015.

[82]SmithWT, LondborgPD, BlomgrenSL, 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.

[83]SoltK, RueschD, FormanSA, 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.

[84]SoltaniF, SayyahM, FeizyF, et al., 2010. A double-blind, placebo-controlled pilot study of ondansetron for patients with obsessive-compulsive disorder. Hum Psychopharmacol, 25(6):509-513.

[85]StefańskiR, PałejkoW, BidzinskiA, 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.

[86]SzeszkoPR, RobinsonD, AlvirJMJ, et al., 1999. Orbital frontal and amygdala volume reductions in obsessive-compulsive disorder. Arch Gen Psychiatry, 56(10):913-919.

[87]TaylorNE, PeiJZ, ZhangJ, 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.

[88]TogaoO, YoshiuraT, NakaoT, 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.

[89]TovoteP, FadokJP, LüthiA, 2015. Neuronal circuits for fear and anxiety. Nat Rev Neurosci, 16(6):317-331.

[90]TovoteP, EspositoMS, BottaP, et al., 2016. Midbrain circuits for defensive behaviour. Nature, 534(7606):206-212.

[91]TseilikmanV, AkulovA, ShevelevO, et al., 2022. Paradoxical anxiety level reduction in animal chronic stress: a unique role of hippocampus neurobiology. Int J Mol Sci, 23(16):9151.

[92]TurnerTJ, MoklerDJ, LuebkeJI, 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.

[93]Urzedo-RodriguesLS, FerreiraHS, SantanaRC, et al., 2014. Blockade of 5-HT3 receptors in the septal area increases Fos expression in selected brain areas. Auton Neurosci, 181:55-68.

[94]Uvnäs-MobergK, HillegaartV, AlsterP, 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.

[95]Vilela-CostaHH, MaraschinJC, CasarottoPC, 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.

[96]VuV, Conant-NorvilleD, 2021. Anxiety: recognition and treatment options. Psychiatr Clin North Am, 44(3):373-380.

[97]YakelJL, JacksonMB, 1988. 5-HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell line. Neuron, 1(7):615-621.

[98]YakelJL, ShaoXM, JacksonMB, 1990. The selectivity of the channel coupled to the 5-HT3 receptor. Brain Res, 533(1):46-52.

[99]ZhaoHY, LinY, ChenSR, et al., 2018. 5-HT3 receptors: a potential therapeutic target for epilepsy. Curr Neuropharmacol, 16(1):29-36.

[100]ZwanzgerP, DomschkeK, BradwejnJ, 2012. Neuronal network of panic disorder: the role of the neuropeptide cholecystokinin. Depress Anxiety, 29(9):762-774.

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