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Involvement of the serotonergic system in the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine in mice

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Abstract

Rationale

Depression is a mental disorder that affects approximately 280 million people worldwide. In the search for new treatments for mood disorders, compounds containing selenium and indolizine derivatives show promising results.

Objectives and methods

To evaluate the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) (0.5–50 mg/kg, intragastric—i.g.) on the tail suspension test (TST) and the forced swim test (FST) in adult male Swiss mice and to elucidate the role of the serotonergic system in this effect through pharmacological and in silico approaches, as well to evaluate acute oral toxicity at a high dose (300 mg/kg).

Results

MeSeI administered 30 min before the FST and the TST reduced immobility time at doses from 1 mg/kg and at 50 mg/kg and increased the latency time for the first episode of immobility, demonstrating an antidepressant-like effect. In the open field test (OFT), MeSeI did not change the locomotor activity. The antidepressant-like effect of MeSeI (50 mg/kg, i.g.) was prevented by the pre-treatment with p-chlorophenylalanine (p-CPA), a selective tryptophan hydroxylase inhibitor (100 mg/kg, intraperitoneally—i.p. for 4 days), with ketanserin, a 5-HT2A/2C receptor antagonist (1 mg/kg, i.p.), and with GR113808, a 5-HT4 receptor antagonist (0.1 mg/kg, i.p.), but not with WAY100635, a selective 5-HT1A receptor antagonist (0.1 mg/kg, subcutaneous—s.c.) and ondansetron, a 5-HT3 receptor antagonist (1 mg/kg, i.p.). MeSeI showed a binding affinity with 5-HT2A, 5 -HT2C, and 5-HT4 receptors by molecular docking. MeSeI (300 mg/kg, i.g.) demonstrated low potential to cause acute toxicity in adult female Swiss mice.

Conclusion

In summary, MeSeI exhibits an antidepressant-like effect mediated by the serotonergic system and could be considered for the development of new treatment strategies for depression.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  • Alkhzem AH, Woodman TJ, Blagbrough IS (2022) Design and synthesis of hybrid compounds as novel drugs and medicines. RSC Adv 12:19470–19484. https://doi.org/10.1039/d2ra03281c

    Article  CAS  Google Scholar 

  • Amigo J, Diaz A, Pilar-Cuellar F, Vidal R, Martin A, Compan V, Pazos A, Castro E (2016) The absence of 5-HT4 receptors modulates depression- and anxiety-like responses and influences the response of fluoxetine in olfactory bulbectomised mice: adaptive changes in hippocampal neuroplasticity markers and 5-HT1A autoreceptor. Neuropharmacology 111:47–58. https://doi.org/10.1016/j.neuropharm.2016.08.037

    Article  CAS  Google Scholar 

  • Anjomshoa M, Boroujeni SN, Bagheri E, Lorigooini Z, Amini-Khoei H (2020) Possible Involvement of N-methyl-D-aspartate Receptor (NMDA-R) in the Antidepressant- like Effect of Trigonelline in Male Mice. Curr Pharm Des 26:5067–5071. https://doi.org/10.2174/1381612826666200610181259

    Article  CAS  Google Scholar 

  • Arterburn D, Sofer T, Boudreau DM, Bogart A, Westbrook EO, Theis MK, Simon G, Haneuse S (2016) Long-term weight change after initiating second-generation antidepressants. J Clin Med 5:48–61. https://doi.org/10.3390/jcm5040048

    Article  CAS  Google Scholar 

  • Bao X, Qi C, Liu T, Zheng X (2021) Information transmission in mPFC-BLA network during exploratory behavior in the open field. Behav Brain Res 414: 113483. https://doi.org/10.1016/j.bbr.2021.113483

  • Baussanne I, Firstova O, Dediu AB, Larosa C, Furdui B, Ghinea IO, Thomas A, Chierici S, Dinica R, Demeunynck M (2021) Interest of novel N-alkylpyridinium-indolizine hybrids in the field of Alzheimer’s disease: synthesis, characterization and evaluation of antioxidant activity, cholinesterase inhibition, and amyloid fibrillation interference. Bioorg Chem 116: 105390. https://doi.org/10.1016/j.bioorg.2021.105390

  • Belal A (2018) Drug likeness, targets, molecular docking and ADMET studies for some indolizine derivatives. Pharmazie 73:635–642. https://doi.org/10.1691/ph.2018.8061

    Article  CAS  Google Scholar 

  • Berg KA, Harvey JA, Spampinato U, Clarke WP (2008) Physiological and therapeutic relevance of constitutive activity of 5-HT 2A and 5-HT 2C receptors for the treatment of depression. Prog Brain Res 172:287–305. https://doi.org/10.1016/S0079-6123(08)00914-X

    Article  CAS  Google Scholar 

  • Bermudez J, Fake CS, Joiner GF, Joiner KA, King FD, Miner WD, Sanger GJ (1990) 5-Hydroxytryptamine (5-HT3) receptor antagonists. 1. Indazole and indolizine-3-carboxylic acid derivatives. J Med Chem 33:1924–1929. https://doi.org/10.1021/jm00169a016

    Article  CAS  Google Scholar 

  • Besckow EM, Nonemacher NT, Garcia CS, da Silva Espíndola CN, Balbom É, Gritzenco F, Savegnago L, Godoi B, Bortolatto CF, Brüning CA (2020) Antidepressant-like effect of a selenopropargylic benzamide in mice: involvement of the serotonergic system. Psychopharmacology (Berl) 237: 3149–3159. https://doi.org/10.1007/s00213-020-05600-1

  • Bhatt S, Nagappa AN, Patil CR (2020) Role of oxidative stress in depression. Drug Discov Today 25:1270–1276. https://doi.org/10.1016/j.drudis.2020.05.001

    Article  CAS  Google Scholar 

  • Birmann PT, Sousa FSS, Domingues M, Brüning CA, Vieira BM, Lenardão EJ, Savegnago L (2019) 3-(4-Chlorophenylselanyl)-1-methyl-1H-indole promotes recovery of neuropathic pain and depressive-like behavior induced by partial constriction of the sciatic nerve in mice. J Trace Elem Med Biol 54:126–133. https://doi.org/10.1016/j.jtemb.2019.04.014

    Article  CAS  Google Scholar 

  • Birmann PT, Casaril AM, Abenante L, Penteado F, Brüning CA, Savegnago L, Lenardão EJ (2022) Neuropharmacology of organoselenium compounds in mental disorders and degenerative diseases. Curr Med Chem. https://doi.org/10.2174/0929867329666220615124412

    Article  Google Scholar 

  • Borroto-Escuela DO, Ambrogini P, Chruścicka B, Lindskog M, Crespo-Ramirez M, Hernández-Mondragón JC, Perez de la Mora M, Schellekens H, Fuxe K (2021) The role of central serotonin neurons and 5-HT heteroreceptor complexes in the pathophysiology of depression: a historical perspective and future prospects. Int J Mol Sci 22:1927–1940. https://doi.org/10.3390/ijms22041927

    Article  CAS  Google Scholar 

  • Carraro Junior LR, Alves AG, Rech TDST, Campos Júnior JC, Siqueira GM, Cunico W, Brüning CA, Bortolatto CF (2021) Three -(pyridin-2-yl)-2-(pyridin-2-ylimino)thiazolidin-4-one as a novel inhibitor of cerebral MAO-B activity with antioxidant properties and low toxicity potential. J Biochem Mol Toxicol 35: e22833. https://doi.org/10.1002/jbt.22833

  • Casaril AM, Domingues M, Lourenço DA, Vieira B, Begnini K, Corcini CD, França RT, Varela Junior AS, Seixas FK, Collares T, Lenardão EJ, Savegnago L (2020) 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole ameliorates long-lasting depression- and anxiogenic-like behaviors and cognitive impairment in post-septic mice: Involvement of neuroimmune and oxidative hallmarks. Chem Biol Interact 331: 109278. doi: https://doi.org/10.1016/j.cbi.2020.109278

  • Castello J, LeFrancois B, Flajolet M, Greengard P, Friedman E, Rebholz H (2018) CK2 regulates 5-HT4 receptor signaling and modulates depressive-like behavior. Mol Psychiatry 23:872–882. https://doi.org/10.1038/mp.2017.240

    Article  CAS  Google Scholar 

  • Chagraoui A, Thibaut F, Skiba M, Thuillez C, Bourin M (2016) 5-HT2C receptors in psychiatric disorders: a review. Prog Neuropsychopharmacol Biol Psychiatry 66:120–135. https://doi.org/10.1016/j.pnpbp.2015.12.006

    Article  CAS  Google Scholar 

  • David DJ, Gardier AM (2016) The pharmacological basis of the serotonin system: application to antidepressant response. Encephale 42:255–263. https://doi.org/10.1016/j.encep.2016.03.012

    Article  CAS  Google Scholar 

  • Dekeyne A, Mannoury la Cour C, Gobert A, Brocco M, Lejeune F, Serres F, Sharp T, Daszuta A, Soumier A, Papp M, Rivet JM, Flik G, Cremers TI, Muller O, Lavielle G, Millan MJ (2008) S32006, a novel 5-HT2C receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models. Psychopharmacology 199:549–568. https://doi.org/10.1007/s00213-008-1177-9

    Article  CAS  Google Scholar 

  • Domingues M, Casaril AM, Smaniotto T, Birmann PT, Lourenço DA, Bampi SR, Vieira B, Lenardão EJ, Savegnago L (2022) Selanylimidazopyridine abolishes inflammation- and stress-induced depressive-like behaviors by modulating the oxido-nitrosative system. Eur J Pharmacol 914: 174570. https://doi.org/10.1016/j.ejphar.2021.174570

  • Dubost E, Dumas N, Fossey C, Magnelli R, Butt-Gueulle S, Ballandonne C, Caignard DH, Dulin F, Sopkova de-Oliveira Santos J, Millet P, Charnay Y, Rault S, Cailly T, Fabis F, (2012) Synthesis and structure-affinity relationships of selective high-affinity 5-HT(4) receptor antagonists: application to the design of new potential single photon emission computed tomography tracers. J Med Chem 55:9693–9707. https://doi.org/10.1021/jm300943r

    Article  CAS  Google Scholar 

  • Eckeli AL, Dach F, Rodrigues AL (2000) Acute treatments with GMP produce antidepressant-like effects in mice. NeuroReport 11:1839–1843. https://doi.org/10.1097/00001756-200006260-00008

    Article  CAS  Google Scholar 

  • Fronza MG, Brod LMP, Casaril AM, Sacramento M, Alves D, Savegnago L (2017) Computational and biological evidences on the serotonergic involvement of SeTACN antidepressant-like effect in mice. PLoS One 12: e0187445. https://doi.org/10.1371/journal.pone.0189975

  • Gall JI, Gonçalves Alves A, Carraro Júnior LR, da Silva Teixeira Rech T, Dos Santos Neto JS, Alves D, Pereira Soares MS, Spohr L, Spanevello RM, Brüning CA, Folharini Bortolatto C (2020) Insights into serotonergic and antioxidant mechanisms involved in antidepressant-like action of 2-phenyl-3-(phenylselanyl)benzofuran in mice. Prog Neuropsychopharmacol Biol Psychiatry 102: 109956. https://doi.org/10.1016/j.pnpbp.2020.109956

  • Gandhimathi A, Sowdhamini R (2016) Molecular modelling of human 5-hydroxytryptamine receptor (5-HT2A) and virtual screening studies towards the identification of agonist and antagonist molecules. J Biomol Struct Dyn 34:952–970. https://doi.org/10.1080/07391102.2015.1062802

    Article  CAS  Google Scholar 

  • Garcia C, Garcia PR, da Silva Espíndola CN, Nunes GD, Jardim NS, Müller SG, Bortolatto CF, Brüning CA (2021) Effect of m-Trifluoromethyl-diphenyl diselenide on the pain-depression dyad induced by reserpine: insights on oxidative stress, apoptotic, and glucocorticoid receptor modulation. Mol Neurobiol 58:5078–5089. https://doi.org/10.1007/s12035-021-02483-x

    Article  CAS  Google Scholar 

  • Garcia CS, Besckow EM, Espíndola CNS, Nunes GD, Zuge NP, de Azeredo MP, Rocha MJD, Carraro Junior LR, Penteado F, Gomes CS, Lenardão EJ, Bortolatto CF, Brüning CA (2022) Antidepressant-like effect of a selenoindolizine in mice: in vivo and in silico evidence for the involvement of the serotonergic 5-HT2A/C receptors. ACS Chem Neurosci 13:1746–1755. https://doi.org/10.1021/acschemneuro.2c00129

    Article  CAS  Google Scholar 

  • Gavioli EC, Vaughan CW, Marzola G, Guerrini R, Mitchell VA, Zucchini S, De Lima TC, Rae GA, Salvadori S, Regoli D, Calo’ G (2004) Antidepressant-like effects of the nociceptin/orphanin FQ receptor antagonist UFP-101: new evidence from rats and mice. Naunyn Schmiedebergs Arch Pharmacol 369:547–553. https://doi.org/10.1007/s00210-004-0939-0

    Article  CAS  Google Scholar 

  • Gill H, Gill B, El-Halabi S, Chen-Li D, Lipsitz O, Rosenblat JD, Van Rheenen TE, Rodrigues NB, Mansur RB, Majeed A, Lui LMW, Nasri F, Lee Y, Mcintyre RS (2020) Antidepressant medications and weight change: a narrative review. Obesity (silver Spring) 28:2064–2072. https://doi.org/10.1002/oby.22969

    Article  Google Scholar 

  • Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR (2012) Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 4:17. https://doi.org/10.1186/1758-2946-4-17

    Article  CAS  Google Scholar 

  • Hao Y, Ge H, Sun M, Gao Y (2019) Selecting an Appropriate Animal Model of Depression. Int J Mol Sci 20:4827–4843. https://doi.org/10.3390/ijms20194827

    Article  CAS  Google Scholar 

  • Jain VK, Priyadarsini KI. Organoselenium compounds in biology and medicine: synthesis, biological and therapeutic treatments. RSC Publishing: London, UK, 2018. ISBN 978-1-78801-029-0

  • Jesse CR, Wilhelm EA, Bortolatto CF, Nogueira CW (2010) Evidence for the involvement of the serotonergic 5-HT2A/C and 5-HT3 receptors in the antidepressant-like effect caused by oral administration of bis selenide in mice. Prog Neuropsychopharmacol Biol Psychiatry 34:294–302. https://doi.org/10.1016/j.pnpbp.2009.11.023

    Article  CAS  Google Scholar 

  • Kimura KT, Asada H, Inoue A, Kadji FMN, Im D, Mori C, Arakawa T, Hirata K, Nomura Y, Nomura N, Aoki J, Iwata S, Shimamura T (2019) Structures of the 5-HT2A receptor in complex with the antipsychotics risperidone and zotepine. Nat Struct Mol Biol 26:121–128. https://doi.org/10.1038/s41594-018-0180-z

    Article  CAS  Google Scholar 

  • Koe BK, Weissman A (1966) p-Chlorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther 154:499–516

    CAS  Google Scholar 

  • Köhler S, Cierpinsky K, Kronenberg G, Adli M (2016) The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants. J Psychopharmacol 30:13–22. https://doi.org/10.1177/0269881115609072

    Article  CAS  Google Scholar 

  • Kopp J, Schwede T (2004) The SWISS-MODEL Repository of annotated three-dimensional protein structure homology models. Nucleic Acids Res 32:D230–D234. https://doi.org/10.1093/nar/gkh008

    Article  CAS  Google Scholar 

  • Lenardão EJ, Santi C, Sancineto L. New frontiers in organoselenium compounds. Springer International Publishing: Cham, Switzerland, 2018. ISBN 978-3-319-92404-5

  • Li G, Wu X, Sun P, Zhang Z, Shao E, Mao J, Cao H, Huang H (2021) Dithiolation indolizine exerts viability suppression effects on A549 cells via triggering intrinsic apoptotic pathways and inducing G2/M phase arrest. Biomed Pharmacother 133: 110961. https://doi.org/10.1016/j.biopha.2020.110961

  • Lian J, Wang J, Sun HF, Lin DZ, Liu H (2013) Application of methyl in drug design. Yao Xue Xue Bao 48:1195–1208

    CAS  Google Scholar 

  • Liu Q, He H, Yang J, Feng X, Zhao F, Lyu J (2020) Changes in the global burden of depression from 1990 to 2017: findings from the Global Burden of Disease study. J Psychiatr Res 126:134–140. https://doi.org/10.1016/j.jpsychires.2019.08.002

    Article  Google Scholar 

  • Lu X, Qi C, Zheng J, Sun M, Jin L, Sun J (2022) The antidepressant effect of deoiled sunflower seeds on chronic unpredictable mild stress in mice through regulation of microbiota-gut-brain axis. Front Nutr 9: 908297. doi: https://doi.org/10.3389/fnut.2022.908297

  • Maffei ME (2020) 5-Hydroxytryptophan (5-HTP): natural occurrence, analysis, biosynthesis, biotechnology, physiology and toxicology. Int J Mol Sci 22: 181:206. 110.3390/ijms22010181

  • Malhi GS, Mann JJ (2018) Depression Lancet 392:2299–2312. https://doi.org/10.1016/S0140-6736(18)31948-2

    Article  Google Scholar 

  • Martin JR, Bös M, Jenck F, Moreau J, Mutel V, Sleight AJ, Wichmann J, Andrews JS, Berendsen HH, Broekkamp CL, Ruigt GS, Köhler C, Delft AM (1998) 5-HT2C receptor agonists: pharmacological characteristics and therapeutic potential. J Pharmacol Exp Ther 286:913–924

    CAS  Google Scholar 

  • Millet R, Domarkas J, Rigo B, Goossens L, Goossens JF, Houssin R, Hénichart JP (2002) Novel potent substance P and neurokinin A receptor antagonists. Conception, synthesis and biological evaluation of indolizine derivatives. Bioorg Med Chem 10:2905–2912. https://doi.org/10.1016/S0968-0896(02)00144-X

    Article  CAS  Google Scholar 

  • Murphy SE, de Cates AN, Gillespie AL, Godlewska BR, Scaife JC, Wright LC, Cowen PJ, Harmer CJ (2021) Translating the promise of 5HT. Psychol Med 51:1111–1120. https://doi.org/10.1017/S0033291720000604

    Article  Google Scholar 

  • Nasehi M, Mohammadi-Mahdiabadi-Hasani MH, Ebrahimi-Ghiri M, Zarrindast MR (2019) Additive interaction between scopolamine and nitric oxide agents on immobility in the forced swim test but not exploratory activity in the hole-board. Psychopharmacology 236:3353–3362. https://doi.org/10.1007/s00213-019-05294-0

    Article  CAS  Google Scholar 

  • Nie L, Wei G, Peng S, Qu Z, Yang Y, Yang Q, Huang X, Liu J, Zhuang Z, Yang X (2017) Melatonin ameliorates anxiety and depression-like behaviors and modulates proteomic changes in triple transgenic mice of Alzheimer’s disease. BioFactors 43:593–611. https://doi.org/10.1002/biof.1369

    Article  CAS  Google Scholar 

  • Nogueira CW, Barbosa NV, Rocha JBT (2021) Toxicology and pharmacology of synthetic organoselenium compounds: an update. Arch Toxicol 95:1179–1226. https://doi.org/10.1007/s00204-021-03003-5

    Article  CAS  Google Scholar 

  • OECD OfECaD (2001) OECD guideline for testing of chemical. In: Acute Oral Toxicity – Acute Toxic Class Method Test No. 423, pp. 1–14

  • Opal MD, Klenotich SC, Morais M (2014) Serotonin 2C receptor antagonists induce fast-onset antidepressant effects. Mol Psychiatry 19:1106–1114. https://doi.org/10.1038/mp.2013.144

    Article  CAS  Google Scholar 

  • Peng Y, McCorvy JD, Harpsoe K, Lansu K, Yuan S, Popov P, Qu L, Pu M, Che T, Nikolajsen LF, Huang XP, Wu Y, Shen L, Bjorn-Yoshimoto WE, Ding K, Wacker D, Han GW, Cheng J, Katritch V, Jensen AA, Hanson MA, Zhao S, Gloriam DE, Roth BL, Stevens RC, Liu ZJ (2018) 5-HT2C receptor structures reveal the structural basis of GPCR polypharmacology. Cell 172: 719–730 e14. https://doi.org/10.1016/j.cell.2018.01.001

  • Penteado F, Gomes CS, Perin G, Garcia CS, Bortolatto CF, Brüning CA, Lenardão EJ (2019) Regioselective Synthesis of 1-Sulfanyl- and 1-Selanylindolizines. J Org Chem 84:7189–7198. https://doi.org/10.1021/acs.joc.9b00871

    Article  CAS  Google Scholar 

  • Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera–a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612. https://doi.org/10.1002/jcc.20084

    Article  CAS  Google Scholar 

  • Pinto Brod LM, Fronza MG, Vargas JP, Lüdtke DS, Luchese C, Wilhelm EA, Savegnago L (2016) Involvement of monoaminergic system in the antidepressant-like effect of (octylseleno)-xylofuranoside in the mouse tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry 65:201–207. https://doi.org/10.1016/j.pnpbp.2015.10.008

    Article  CAS  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    CAS  Google Scholar 

  • Qu SY, Li XY, Heng X, Qi YY, Ge PY, Ni SJ, Yao ZY, Guo R, Yang NY, Cao Y, Zhang QC, Zhu HX (2021) Analysis of antidepressant activity of Huang-Lian Jie-Du decoction through network pharmacology and metabolomics. Front Pharmacol 12: 619288. https://doi.org/10.3389/fphar.2021.619288

  • Rebholz H, Friedman E, Castello J (2018) Alterations of expression of the serotonin 5-HT4 receptor in brain disorders. Int J Mol Sci 19:1581–3601. https://doi.org/10.3390/ijms19113581

    Article  CAS  Google Scholar 

  • Rech T, Gonçalves Alves A, Nornberg Strelow D, Devantier Krüger L, Carraro Júnior LR, Dos Santos Neto JS, Braga AL, Brüning CA, Folharini Bortolatto C (2021) 2-Phenyl-3-(phenylselanyl)benzofuran elicits acute antidepressant-like action in male Swiss mice mediated by modulation of the dopaminergic system and reveals therapeutic efficacy in both sexes. Psychopharmacology 238:3013–3024. https://doi.org/10.1007/s00213-021-05921-9

    Article  CAS  Google Scholar 

  • Redrobe JP, Bourin M, Colombel MC, Baker GB (1998) Dose-dependent noradrenergic and serotonergic properties of venlafaxine in animal models indicative of antidepressant activity. Psychopharmacology 138:1–8. https://doi.org/10.1007/s002130050638

    Article  CAS  Google Scholar 

  • Rosenzweig-Lipson S, Sabb A, Stack G, Mitchell P, Lucki I, Malberg JE, Grauer S, Brennan J, Cryan JF, Sukoff Rizzo SJ, Dunlop J, Barrett JE, Marquis KL (2007) Antidepressant-like effects of the novel, selective, 5-HT2C receptor agonist WAY-163909 in rodents. Psychopharmacology 192:159–170. https://doi.org/10.1007/s00213-007-0710-6

    Article  CAS  Google Scholar 

  • Samuels BA, Mendez-David I, Faye C (2016) Serotonin 1A and serotonin 4 receptors. Neuroscientist 22:26–45. https://doi.org/10.1177/1073858414561303

    Article  CAS  Google Scholar 

  • Serretti A, Mandelli L (2010) Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 71:1259–1272. https://doi.org/10.4088/JCP.09r05346blu

    Article  Google Scholar 

  • Sharma V, Kumar V, Pathak D (2010) Biological importance of the indole nucleus in recent years: a comprehensive review. J Heterocyclic Chem 47:491–502. https://doi.org/10.1002/jhet.349

    Article  CAS  Google Scholar 

  • Sharma V, Kumar V, Kumar P (2013) Heterocyclic chalcone analogues as potential anticancer agents. Anticancer Agents Med Chem 13:422–432

    CAS  Google Scholar 

  • Sousa FSS, Birmann PT, Baldinotti R, Fronza MG, Balaguez R, Alves D, Brüning CA, Savegnago L (2018) α- (phenylselanyl) acetophenone mitigates reserpine-induced pain depression dyad: behavioral, biochemical and molecular docking evidences. Brain Res Bull 142:129–137. https://doi.org/10.1016/j.brainresbull.2018.07.007

    Article  CAS  Google Scholar 

  • Sousa FSS, Birmann PT, Bampi SR, Fronza MG, Balaguez R, Alves D, Leite MR, Nogueira CW, Brüning CA, Savegnago L (2019) Lipopolysaccharide-induced depressive-like, anxiogenic-like and hyperalgesic behavior is attenuated by acute administration of α-(phenylselanyl) acetophenone in mice Neuropharmacology 1, 146, 128–137. https://doi.org/10.1016/j.neuropharm.2018.11.028

  • Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370. https://doi.org/10.1007/BF00428203

    Article  CAS  Google Scholar 

  • Sun S, Fu J (2018) Methyl-containing pharmaceuticals: Methylation in drug design. Bioorg Med Chem Lett 28:3283–3289. https://doi.org/10.1016/j.bmcl.2018.09.016

    Article  CAS  Google Scholar 

  • Szopa A, Herbet M, Poleszak E, Bogatko K, Ostrowska-Leśko M, Świąder K, Szponar J, Serefko A (2022) Effects of selen on the antidepressant-like activity of agents affecting the adenosinergic neurotransmission. Metabolites 12. https://doi.org/10.3390/metabo12070586

  • Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461. https://doi.org/10.1002/jcc.21334

    Article  CAS  Google Scholar 

  • Venugopala KN, Chandrashekharappa S, Tratrat C, Deb PK, Nagdeve RD, Nayak SK, Morsy MA, Borah P, Mahomoodally FM, Mailavaram RP, Attimarad M, Aldhubiab BE, Sreeharsha N, Nair AB, Alwassil OI, Haroun M, Mohanlall V, Shinu P, Venugopala R, Kandeel M, Nandeshwarappa BP, Ibrahim YF (2021) Crystallography, molecular modeling, and COX-2 inhibition studies on indolizine derivatives. Molecules 26:3550–3570. https://doi.org/10.3390/molecules26123550

    Article  CAS  Google Scholar 

  • Villas-Boas GR, Lavorato SN, Paes MM, de Carvalho PMG, Rescia VC, Cunha MS, de Magalhães-Filho MF, Ponsoni LF, de Carvalho AAV, de Lacerda RB, da S Leite L, da S Tavares-Henriques M, Lopes LAF, Oliveira LGR, Silva-Filho SE, da Silveira APS, Cuman RKN, de S Silva-Comar FM, Comar JF, do A Brasileiro L, Dos Santos JN, de Freitas WR, Leão KV, da Silva JG, Klein RC, Klein MHF, da S Ramos BH, Fernandes CKC, de L Ribas DG, Oesterreich SA (2021) Modulation of the serotonergic receptosome in the treatment of anxiety and depression: a narrative review of the experimental evidence. Pharmaceuticals (Basel) 14: 148-191.https://doi.org/10.3390/ph14020148

  • Vitaku E, Smith DT, Njardarson JT (2014) Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J Med Chem 57:10257–10274. https://doi.org/10.1021/jm501100b

    Article  CAS  Google Scholar 

  • Walsh RN, Cummins RA (1976) The Open-Field Test: a critical review. Psychol Bull 83:482–504

    Article  CAS  Google Scholar 

  • Wang Q, Timberlake MA, Prall K, Dwivedi Y (2017) The recent progress in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry 77:99–109. https://doi.org/10.1016/j.pnpbp.2017.04.008

    Article  Google Scholar 

  • Wang J, Um P, Dickerman BA, Liu J (2018) Zinc, magnesium, selenium and depression: a review of the evidence, potential mechanisms and implications. Nutrients 10:584. https://doi.org/10.3390/nu10050584

    Article  CAS  Google Scholar 

  • Wang YQ, Lin WW, Wu N, Wang SY, Chen MZ, Lin ZH, Xie XQ, Feng ZW (2019) Structural insight into the serotonin (5-HT) receptor family by molecular docking, molecular dynamics simulation and systems pharmacology analysis. Acta Pharmacol Sin 40:1138–1156. https://doi.org/10.1038/s41401-019-0217-9

    Article  CAS  Google Scholar 

  • WHO (2021) Depression. World Health Organization. IOP Publishing PhysicsWeb. https://www.who.int/news-room/fact-sheets/detail/depression Accessed on February 04 2022

  • Xue Y, Tang J, Ma X, Li Q, Xie B, Hao Y, Jin H, Wang K, Zhang G, Zhang L (2016) Synthesis and biological activities of indolizine derivatives as alpha-7 nAChR agonists. Eur J Med Chem 115:94–108. https://doi.org/10.1016/j.ejmech.2016.03.016

    Article  CAS  Google Scholar 

  • Yuen H, Hung A, Yang AWH, Lenon GB (2020) Mechanisms of action of cassiae semen for weight management: a computational molecular docking study of serotonin receptor 5-HT2C. Int J Mol Sci 21:1326–1344. https://doi.org/10.3390/ijms21041326

    Article  CAS  Google Scholar 

  • Zięba A, Stępnicki P, Matosiuk D, Kaczor AA (2021) Overcoming depression with 5-HT. Int J Mol Sci 23:10–27. https://doi.org/10.3390/ijms23010010

    Article  CAS  Google Scholar 

  • Zuo Z, Chen G, Luo X, Puah C, Zhu W, Chen K, Jiang H (2007) Pharmacophore-directed homology modeling and molecular dynamics simulation of G protein-coupled receptor: study of possible binding modes of 5-HT2C receptor agonists. Acta Biochim Biophys Sin (shanghai) 39:413–422. https://doi.org/10.1111/j.1745-7270.2007.00295.x

    Article  CAS  Google Scholar 

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Funding

The experiments were financed by the Coordenação de Aperfeiçoamento Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant numbers 420386/2018–1 and 438384/2018–0), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, grant numbers 21/2551–0000728-1 and 21/2551–0000614-5).

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Authors and Affiliations

  1. Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), Capão Do Leão Campus, Pelotas, RS, 96010-900, Brazil

    Marcia Juciele da Rocha, Camila Simões Pires, Marcelo Heinemann Presa, Evelyn Mianes Besckow, Gustavo D’Avila Nunes, Cristiani Folharini Bortolatto & César Augusto Brüning

  2. Clean Organic Synthesis Laboratory (LASOL), Postgraduate Program in Chemistry (PPGQ), Center of Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), Capão Do Leão Campus, Pelotas, RS, 96010-900, Brazil

    Caroline Signorini Gomes, Filipe Penteado & Eder João Lenardão

Authors
  1. Marcia Juciele da Rocha
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  2. Camila Simões Pires
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  3. Marcelo Heinemann Presa
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  4. Evelyn Mianes Besckow
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  5. Gustavo D’Avila Nunes
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  9. Cristiani Folharini Bortolatto
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  10. César Augusto Brüning
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Contributions

MJR, CFB, and CAB conceptualized, designed, validated, and supervised the study. CAB, CFB, and EJL acquired funds. CAB, CFB, and EJL edited and revised the manuscript. FP and CSG synthesized and characterized MeSeI. MJR, CSP, MHP, EMB, and GDN performed the literature review and statistical analyses, interpreted the results, and wrote the manuscript. EMB performed the molecular docking. MJR, CSP, MHP, and GDN conducted in vivo experiments.

Corresponding authors

Correspondence to Cristiani Folharini Bortolatto or César Augusto Brüning.

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da Rocha, M.J., Pires, C.S., Presa, M.H. et al. Involvement of the serotonergic system in the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine in mice. Psychopharmacology 240, 373–389 (2023). https://doi.org/10.1007/s00213-023-06313-x

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