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Metabolic Brain Disease

, Volume 34, Issue 5, pp 1375–1384 | Cite as

The faster-onset antidepressant effects of hypidone hydrochloride (YL-0919)

  • Li-jun Sun
  • Li-ming Zhang
  • Dan Liu
  • Rui Xue
  • Yan-qin Liu
  • Lei Li
  • Ying Guo
  • Chao Shang
  • Jun-qi Yao
  • You-zhi ZhangEmail author
  • Yun-feng LiEmail author
Original Article
  • 77 Downloads

Abstract

Hypidone hydrochloride (YL-0919), is a novel structural antidepressant candidate as a triple selective serotonin re-uptake inhibitor (SSRI), 5-HT1A partial agonist and 5-HT6 agonist. Here, we investigated the rapid onset antidepressant-like effects of YL-0919 and the possible mechanism in rats exposed to a chronic unpredictable stress (CUS) paradigm. In the CUS rats, it was found that fluoxetine (FLX, 10 mg/kg) treatment exerted antidepressant actions on 20-22d, while YL-0919 or vilazodone (VLZ, a dual 5-HT1A partial agonist and SSRI) administrated once daily exerted faster antidepressant-like behaviors [4 days in the sucrose preference test (SPT) and 6 days in the novelty suppressed feeding test (NSF)]. Thereafter, the serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels were reversed by treatment with YL-0919 for 7 days. Furthermore, YL-0919 treatment for 5 days reversed the brain derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling and the key synaptic proteins, such as post-synaptic density (PSD95), GluR1 and presynaptic protein synapsin1. Meanwhile, the dendritic complexity of pyramidal neurons in prefrontal cortex (PFC) were also increased in the CUS rats. These data suggest that YL-0919 exerts a faster antidepressant-like effect on behaviors and this effect maybe at least partially mediated by the BDNF-mTOR signaling related dendritic complexity increase in the PFC.

Keywords

Hypidone hydrochloride Antidepressant Faster-onset Prefrontal cortex Dendritic complexity 

Notes

Acknowledgements

This work was supported by the National Key New Drug Creation Program of China (No.2017ZX09309012) and the National Natural Science Foundation of China (No.81773703).

Compliance with ethical standards

Conflict of interest

None of the authors had conflict of interest to declare.

References

  1. Artigas F, Celada P, Laruelle M, Adell A (2001) How does pindolol improve antidepressant action? Trends Pharmacol Sci 22:224–228CrossRefGoogle Scholar
  2. Bekris S, Antoniou K, Daskas S, Papadopoulou-Daifoti Z (2005) Behavioural and neurochemical effects induced by chronic mild stress applied to two different rat strains. Behav Brain Res 161:45–59CrossRefGoogle Scholar
  3. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354CrossRefGoogle Scholar
  4. Bodnoff SR, Suranyi-Cadotte B, Aitken DH, Quirion R, Meaney MJ (1988) The effects of chronic antidepressant treatment in an animal model of anxiety. Psychopharmacology 95:298–302CrossRefGoogle Scholar
  5. Cassani J, Dorantes-Barron AM, Novales LM, Real GA, Estrada-Reyes R (2014) Anti-depressant-like effect of kaempferitrin isolated from Justicia spicigera Schltdl (Acanthaceae) in two behavior models in mice: evidence for the involvement of the serotonergic system. Molecules. 19:21442–21461CrossRefGoogle Scholar
  6. Celada P, Puig MV, Artigas F (2013) Serotonin modulation of cortical neurons and networks. Front Integr Neurosci 7:1–20CrossRefGoogle Scholar
  7. Chen HX, Jin ZL, Zhang LM, Xue R, Xu XD, Zhao N, Qiu ZK, Wang XW, Zhang YZ, Yang RF, Li YF (2013) Antidepressant-like activity of YL-0919: a novel combined selective serotonin reuptake inhibitor and 5-HT1A receptor agonist. PLoS One 8:e83271.  https://doi.org/10.1371/journal.pone.0083271 CrossRefGoogle Scholar
  8. Chen XF, Jin ZL, Gong Y, Zhao N, Wang XY, Ran YH, Zhang YZ, Zhang LM, Li YF (2018) 5-HT6 receptor agonist and memory-enhancing properties of hypidone hydrochloride (YL-0919), a novel 5-HT1A receptor partial agonist and SSRI. Neuropharmacology 138:1–9CrossRefGoogle Scholar
  9. Dawson LA, Watson JM (2009) Vilazodone: a 5-HT1A receptor agonist/serotonin transporter inhibitor for the treatment of affective disorders. CNS Neurosci Ther 15:107–117CrossRefGoogle Scholar
  10. du Jardin KG, Müller HK, Sanchez C, Wegener G, Elfving B (2016) A single dose of vortioxetine, but not ketamine or fluoxetine, increases plasticity-related gene expression in the rat frontal cortex. Eur J Pharmacol 786:29–35CrossRefGoogle Scholar
  11. Duman RS (2014) Neurobiology of stress, depression, and rapid acting antidepressants: remodeling synaptic connections. Depress Anxiety 6:1–6Google Scholar
  12. Duman RS, Aghajanian GK (2012) Synaptic dysfunction in depression: potential therapeutic targets. Science 338:68–72CrossRefGoogle Scholar
  13. Dwyer JM, Duman RS (2013) Activation of mammalian target of rapamycin and synaptogenesis: role in the actions of rapid-acting antidepressants. Biol Psychiatry 73:1189–1198CrossRefGoogle Scholar
  14. Dwyer JM, Lepack AE, Duman RS (2013) mGluR2/3 blockade produces rapid and long-lasting reversal of anhedonia caused by chronic stress exposure. J Mol Psychiatr 1:1–4CrossRefGoogle Scholar
  15. Flores G, Alquicer G, Silva-Gomez AB, Zaldivar G, Stewart J, Quirion R, Srivastava LK (2005) Alterations in dendritic morphology of prefrontal cortical and nucleus accumbens neurons in post-pubertal rats after neonatal excitotoxic lesions of the ventral hippocampus. Neuroscience 133:463–470CrossRefGoogle Scholar
  16. Garcia-Garcia AL, Navarro-Sobrino M, Pilosof G, Banerjee P, Dranovsky A, Leonardo ED (2016) 5-HT1A agonist properties contribute to a robust response to Vilazodone in the novelty suppressed feeding paradigm. Int J Neuropsychopharmacol 19:1–8CrossRefGoogle Scholar
  17. Glazer WM (2011) A new antidepressant. Behav Healthc 31:39–40Google Scholar
  18. Grippo AJ, Beltz TG, Weiss RM, Johnson AK (2006) The effects of chronic fluoxetine treatment on chronic mild stress-induced cardiovascular changes and anhedonia. Biol Psychiatry 59:309–316CrossRefGoogle Scholar
  19. Hashimoto K (2015) Inflammatory biomarkers as differential predictors of antidepressant response. Int J Mol Sci 16:7796–7801CrossRefGoogle Scholar
  20. Hopkins CR (2011) ACS chemical neuroscience molecule spotlight on viibryd (vilazodone). ACS Chem Neurosci 2:554CrossRefGoogle Scholar
  21. Kraus C, Castrén E, Kasper S, Lanzenberger R (2017) Serotonin and neuroplasticity–links between molecular, functional and structural pathophysiology in depression. Neurosci Biobehav Rev 77:317–326CrossRefGoogle Scholar
  22. Lee CC, Huang CC, Wu MY, Hsu KS (2005) Insulin stimulates postsynaptic density-95 protein translation via the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway. J Biol Chem 280:18543–18550CrossRefGoogle Scholar
  23. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonist. Science 329:959–964CrossRefGoogle Scholar
  24. Li YF, Cheng YF, Huang Y, Conti M, Wilson SP, O’Donnell JM, Zhang HT (2011a) Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling. J Neurosci 31:172–183CrossRefGoogle Scholar
  25. Li YF, Cheng YF, Huang Y, Conti M, Wilson SP, O'Donnell JM, Zhang HT (2011b) Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling. J Neurosci 3:172–183CrossRefGoogle Scholar
  26. Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY (2011c) Aghajanian G, Duman RS, glutamate N-methyl-d-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 69:754–761CrossRefGoogle Scholar
  27. Li Y, Sanchez C, Gulinello M (2017) Distinct antidepressant-like and cognitive effects of antidepressants with different mechanisms of action in middle-aged female mice. Int J Neuropsychopharmacol 20:510–515CrossRefGoogle Scholar
  28. Li XT, Wu T, Yu ZH, Li TT, Zhang JS, Zhang ZN, Cai M, Zhang W, Xiang J, Cai DF (2018) Apocynum venetum leaf extract reverses depressive-like behaviors in chronically stressed rats by inhibiting oxidative stress and apoptosis. Biomed Pharmacother 100:394–406CrossRefGoogle Scholar
  29. Liebrenz M, Borgeat A, Leisinger R, Stohler R (2007) Intravenous ketamine therapy in a patient with a treatment-resistant major depression. Swiss Med Wkly 137:234–236Google Scholar
  30. Mahmoud R, Wainwright SR, Chaiton JA, Lieblich SE, Galea LAM (2016) Ovarian hormones, but not fluoxetine, impart resilience within a chronic unpredictable stress model in middle-aged female rats. Neuropharmacology 107:278–293CrossRefGoogle Scholar
  31. Masi G, Brovedani P (2011) The hippocampus, neurotrophic factors and depression possible implications for the pharmacotherapy of depression. CNS Drugs 25:913–931CrossRefGoogle Scholar
  32. Montgomery SA (1997) Suicide and antidepressants. Ann N Y Acad Sci 836:329–338CrossRefGoogle Scholar
  33. Niciu MJ, Henter ID, Luckenbaugh DA, Zarate CA, Charney DS (2014) Glutamate receptor antagonists as fast-acting therapeutic alternatives for the treatment of depression: ketamine and other compounds. Annu Rev Pharmacol Toxicol 54:119–139CrossRefGoogle Scholar
  34. Papp M (1998) Models of affective illness: chronic mild stress in the rat. Curr Protoc Pharmacol 57:5.9.1–5.9.11Google Scholar
  35. Partar OL, Belmer A, Holgate JY, Klenowski PM, Bartlett SE (2018) Modulation of serotonin and noradrenaline in the BLA by pindolol reduces long-term ethanol intake. Addict Biol:1–11.  https://doi.org/10.1111/adb.12630
  36. Perez-Caballero L, Torres-Sanchez S, Bravo L, Mico JA, Berrocoso E (2014) Fluoxetine: a case history of its discovery and preclinical development. Expert Opin Drug Discovery 9:567–578CrossRefGoogle Scholar
  37. Pham TH, Mendez-David I, Defaix C, Guiard BP, Tritschler L, David DJ, Gardier AM (2017) Ketamine treatment involves medial prefrontal cortex serotonin to induce a rapid antidepressant-like activity in BALB/cJ mice. Neuropharmacology 112:198–209CrossRefGoogle Scholar
  38. Popoli M, Yan Z, McEwen B, Sanacora G (2012) The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 13:22–37CrossRefGoogle Scholar
  39. Qin JJ, Chen HX, Zhao N, Yuan L, Zhang YZ, Yang RF, Zhang LM, Li YF (2014) The role of activation of the 5-HT1A receptor and adenylate cyclase in the antidepressant-like effect of YL-0919, a dual 5-HT1A agonist and selective serotonin reuptake inhibitor. Neurosci Lett 582:104–108CrossRefGoogle Scholar
  40. Ran YH, Hu XX, Wang YL, Zhao N, Zhang LM, Liu HX, Li YF (2018) YL-0919, a dual 5-HT1A partial agonist and SSRI, produces antidepressant-and anxiolytic-like effects in rats subjected to chronic unpredictable stress. Acta Pharmacol Sin 39:12–23CrossRefGoogle Scholar
  41. Rickels K, Athanasiou M, Robinson DS, Gibertini M, Whalen H, Reed CR (2009) Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 70:326–333CrossRefGoogle Scholar
  42. Savitz J, Lucki I, Drevets WC (2009) 5-HT(1A) receptor function in major depressive disorder. Prog Neurobiol 88:17–31CrossRefGoogle Scholar
  43. Schratt GM, Nigh EA, Chen WG, Hu L, Greenberg ME (2004) BDNF regulates the translation of a select group of mRNAs by a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway during neuronal development. J Neurosci 24:7366–7377CrossRefGoogle Scholar
  44. Shi L, Wang J, Xu S, Lu Y (2016) Efficacy and tolerability of vilazodone for major depressive disorder: evidence from phase iii/iV randomized controlled trials. Drug Des. Dev Ther 10:3899–3907CrossRefGoogle Scholar
  45. Sholl DA (1953) Dendritic organization in the neurons of the visual and motor. Cortices of the cat. J Anat 87:387–406Google Scholar
  46. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M, STAR*D Study Team (2006) Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 163:28–40CrossRefGoogle Scholar
  47. Van Amsterdam C, Seyfried CA (2014) Mechanism of action of the bimodal antidepressant vilazodone: evidence for serotonin1A-receptor-mediated auto-augmentation of extracellular serotonin output. Psychopharmacology 231:2547–2558Google Scholar
  48. Wang JW, David DJ, Monckton JE, Battaglia F, Hen R (2008) Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci 28:1374–1384CrossRefGoogle Scholar
  49. Wang ZZ, Zhang Y, Liu YQ, Zhao N, Zhang YZ, Yuan L, An L, Li J, Wang XY, Qin JJ, Wilson SP, O’Donnell JM, Zhang HT, Li YF (2013) RNA interference-mediated phosphodiesterase 4D splice variants knock-down in the prefrontal cortex produces antidepressant-like and cognition-enhancing effects. Br J Pharmacol 168:1001–1014CrossRefGoogle Scholar
  50. Wang W, Zhang LM, Zhang XY, Xue R, Li L, Zhao W, Fu Q, Mi W, Li Y (2016) Lentiviral-mediated overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus ameliorates LPS-induced cognitive impairment in mice. Front Pharmacol 7:384–395Google Scholar
  51. Warner-Schmidt JL, Duman RS (2007) VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. PNAS 104:4647–4652CrossRefGoogle Scholar
  52. Willner P, Muscat R, Papp M (1992) Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 16:525–534CrossRefGoogle Scholar
  53. Yang C, Hu Y, Zhou Z, Zhang GF, Yang JJ (2013) Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test. Ups J Med Sci 118:3–8CrossRefGoogle Scholar
  54. Yang C, Shirayama Y, Zhang JC, Ren Q, Yao W, Ma M, Dong C, Hashimoto K (2015) R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Transl Psychiatry 5:1–11CrossRefGoogle Scholar
  55. Yong CB, Chen T, Nusslock R, Keller J, Schatzberg AF, Menon V (2016) Anhedonia and general distress show dissociable ventromedial prefrontal cortex connectivity in major depressive disorder. Transl Psychiatry 6:1–11Google Scholar
  56. Zhang LM, Wang XY, Zhao N, Wang YL, Hu XX, Ran YH, Liu YQ, Zhang YZ, Yang RF, Li YF (2017) Neurochemical and behavioural effects of hypidone hydrochloride (YL-0919): a novel combined selective 5-HT reuptake inhibitor and partial 5-HT1A agonist. Br J Pharmacol 174:769–780CrossRefGoogle Scholar
  57. Zhao WX, Zhang JH, Cao JB, Wang W, Wang DX, Zhang XY, Yu J, Zhang YY, Zhang YZ, Mi WD (2017) Acetaminophen attenuates lipopolysaccharide- induced cognitive impairment through antioxidant activity. J Neuroinflammation 14:17–31CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Li-jun Sun
    • 1
  • Li-ming Zhang
    • 1
  • Dan Liu
    • 2
  • Rui Xue
    • 1
  • Yan-qin Liu
    • 1
  • Lei Li
    • 3
  • Ying Guo
    • 4
  • Chao Shang
    • 1
  • Jun-qi Yao
    • 1
  • You-zhi Zhang
    • 1
    Email author
  • Yun-feng Li
    • 1
    Email author
  1. 1.Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Institute of Pharmacology and ToxicologyBeijingChina
  2. 2.Central Blood Station of HengshuiHengshuiChina
  3. 3.Department of AnesthesiologyBeijing Chuiyangliu HospitalBeijingChina
  4. 4.Department of AnesthesiologyGeneral Hospital of PLABeijingChina

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