Metabolic Brain Disease

, Volume 31, Issue 2, pp 455–463 | Cite as

Echinocystic acid reduces reserpine-induced pain/depression dyad in mice

  • Shuo Li
  • Jing Han
  • Dong-sheng Wang
  • Bin Feng
  • Ya-ting Deng
  • Xin-shang Wang
  • Qi Yang
  • Ming-gao Zhao
Original Article
First Online:
Received:
Accepted:

Abstract

Chronic pain has consistently been correlated with depression. Echinocystic acid (EA), a natural triterpone enriched in various herbs and used for medicinal purpose in many Asian countries, exhibits anti-inflammatory and analgesic activities. However, little is known the effects of EA on the depression. In present study, we investigated the anti-depression activities in the mouse model of reserpine-induced pain-depression dyad. Reserpine (1 mg/kg subcutaneously daily for 3 days) caused significant depression-like behaviors and pain sensation. Subsequent treatment of EA (5 mg/kg intragastrically daily for 5 days) attenuated the reserpine-induced pain/depression dyad as shown by the increase of pain threshold and the behaviors in forced swimming test, tail suspension test, and open field test. Furthermore, treatment of EA reversed the decrease of biogenic amines (norepinephrine, dopamine, and serotonin) in the brain region of hippocampus, a structure involved in the formation of emotional disorders. Levels of serotonin receptor 5-HT1A were decreased and levels of 5-HT2A were increased in the reserpine-injected mice. Treatment of EA could restore the alterations of serotonin receptors. At the same time, the increase in GluN2B-containing NMDA receptors, p-GluA1-Ser831, PSD-95 and CaMKII were integrated with the increase in caspase-3 and iNOS levels in the hippocampus of the reserpine-injected mice. EA significantly reversed the changes of above proteins. However, EA did not affect the levels of GluN2A-containing NMDA receptors and the total levels of GluA1 and p-GluA1-Ser845. Our study provides strong evidence that EA attenuates reserpine-induced pain/depression dyad partially through regulating the biogenic amines levels and GluN2B receptors in the hippocampus.

Keywords

Echinocystic acid Pain Depression NMDA receptor Serotonin Hippocampus 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This research was supported by National Natural Science Foundation of China, No. 31271144, 31325022, and 2013DFG32650.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Albert PR, Lemonde S (2004) 5-HT1A receptors, gene repression, and depression: guilt by association. Neuroscientist: Rev J Bringing Neurobiol Neurol Psychiatry 10:575–593CrossRefGoogle Scholar
  2. Antkiewicz-Michaluk L, Wasik A, Mozdzen E, Romanska I, Michaluk J (2014) Antidepressant-like effect of tetrahydroisoquinoline amines in the animal model of depressive disorder induced by repeated administration of a low dose of reserpine: behavioral and neurochemical studies in the rat. Neurotox Res 26:85–98CrossRefPubMedPubMedCentralGoogle Scholar
  3. Arora V, Kuhad A, Tiwari V, Chopra K (2011) Curcumin ameliorates reserpine-induced pain-depression dyad: behavioural, biochemical, neurochemical and molecular evidences. Psychoneuroendocrinology 36:1570–1581CrossRefPubMedGoogle Scholar
  4. Blier P, Abbott FV (2001) Putative mechanisms of action of antidepressant drugs in affective and anxiety disorders and pain. J Psychiatry Neurosci 26:37–43PubMedPubMedCentralGoogle Scholar
  5. Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39CrossRefPubMedGoogle Scholar
  6. Bourin M, Mocaer E, Porsolt R (2004) Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors. J Psychiatry Neurosci 29:126–133PubMedPubMedCentralGoogle Scholar
  7. Cates LN, Roberts AJ, Huitron-Resendiz S, Hedlund PB (2013) Effects of lurasidone in behavioral models of depression. Role of the 5-HT(7) receptor subtype. Neuropharmacology 70:211–217CrossRefPubMedGoogle Scholar
  8. Celada P, Puig M, Amargos-Bosch M, Adell A, Artigas F (2004) The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci 29:252–265PubMedPubMedCentralGoogle Scholar
  9. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55–63CrossRefPubMedGoogle Scholar
  10. Chen J et al (2015) Antidepressant-like effects of ferulic acid: involvement of serotonergic and norepinergic systems. Metab Brain Dis 30:129–136CrossRefPubMedGoogle Scholar
  11. De Benedetto GE et al (2014) A rapid and simple method for the determination of 3,4-dihydroxyphenylacetic acid, norepinephrine, dopamine, and serotonin in mouse brain homogenate by HPLC with fluorimetric detection. J Pharm Biomed Anal 98:266–270CrossRefPubMedGoogle Scholar
  12. Dellarole A et al (2014) Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling. Brain Behav Immun 41:65–81CrossRefPubMedGoogle Scholar
  13. Drevets WC, Thase ME, Moses-Kolko EL, Price J, Frank E, Kupfer DJ, Mathis C (2007) Serotonin-1A receptor imaging in recurrent depression: replication and literature review. Nucl Med Biol 34:865–877CrossRefPubMedPubMedCentralGoogle Scholar
  14. Dutta A, McKie S, Deakin JF (2015) Ketamine and other potential glutamate antidepressants. Psychiatry Res 225:1–13CrossRefPubMedGoogle Scholar
  15. Elhwuegi AS (2004) Central monoamines and their role in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry 28:435–451CrossRefGoogle Scholar
  16. Fasick V, Spengler RN, Samankan S, Nader ND, Ignatowski TA (2015) The hippocampus and TNF: common links between chronic pain and depression. Neurosci Biobehav Rev 53:139–159. doi: 10.1016/j.neubiorev.2015.03.014 CrossRefPubMedGoogle Scholar
  17. Gene RM, Cartana C, Adzet T, Marin E, Parella T, Canigueral S (1996) Anti-inflammatory and analgesic activity of Baccharis trimera: identification of its active constituents. Planta Med 62:232–235CrossRefPubMedGoogle Scholar
  18. Guiard BP, El Mansari M, Blier P (2009) Prospect of a dopamine contribution in the next generation of antidepressant drugs: the triple reuptake inhibitors. Curr Drug Targets 10:1069–1084CrossRefPubMedGoogle Scholar
  19. Guo YY et al (2012) Acute stress induces down-regulation of large-conductance Ca2+−activated potassium channels in the lateral amygdala. J Physiol 590:875–886CrossRefPubMedPubMedCentralGoogle Scholar
  20. Joh EH, Gu W, Kim DH (2012) Echinocystic acid ameliorates lung inflammation in mice and alveolar macrophages by inhibiting the binding of LPS to TLR4 in NF-kappaB and MAPK pathways. Biochem Pharmacol 84:331–340CrossRefPubMedGoogle Scholar
  21. Joh EH, Jeong JJ, Kim DH (2014) Inhibitory effect of echinocystic acid on 12-O-tetradecanoylphorbol-13-acetate-induced dermatitis in mice. Arch Pharm Res 37:225–231CrossRefPubMedGoogle Scholar
  22. Karolewicz B, Szebeni K, Gilmore T, Maciag D, Stockmeier CA, Ordway GA (2009) Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression. Int J neuropsychopharmacol Off Sci J Collegium Int Neuropsychopharmacol 12:143–153Google Scholar
  23. Khoshnoodi M, Fakhraei N, Dehpour AR (2015) Possible involvement of nitric oxide in antidepressant-like effect of silymarin in male mice. Pharm Biol 53:739–745CrossRefPubMedGoogle Scholar
  24. Lacivita E, Di Pilato P, De Giorgio P, Colabufo NA, Berardi F, Perrone R, Leopoldo M (2012) The therapeutic potential of 5-HT1A receptors: a patent review. Exp Opin Ther Pat 22:887–902CrossRefGoogle Scholar
  25. Li K et al (2013) betaCaMKII in lateral habenula mediates core symptoms of depression. Science 341:1016–1020CrossRefPubMedPubMedCentralGoogle Scholar
  26. Liu SB et al (2014) Attenuation of reserpine-induced pain/depression dyad by gentiopicroside through downregulation of GluN2B receptors in the amygdala of mice. Neuromol Med 16:350–359CrossRefGoogle Scholar
  27. Molosh AI, Sajdyk TJ, Truitt WA, Zhu W, Oxford GS, Shekhar A (2013) NPY Y1 receptors differentially modulate GABAA and NMDA receptors via divergent signal-transduction pathways to reduce excitability of amygdala neurons. Neuropsychopharmacol Off Publ Ame Coll Neuropsychopharmacol 38:1352–1364CrossRefGoogle Scholar
  28. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12:529–540CrossRefPubMedGoogle Scholar
  29. Murata Y, Yanagihara Y, Mori M, Mine K, Enjoji M (2015) Chronic treatment with tandospirone, a serotonin 1A receptor partial agonist, inhibits psychosocial stress-induced changes in hippocampal neurogenesis and behavior. J Affect Disord 180:1–9CrossRefPubMedGoogle Scholar
  30. Niciu MJ, Ionescu DF, Richards EM, Zarate CA Jr (2014) Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder. J Neural Transm 121:907–924CrossRefPubMedPubMedCentralGoogle Scholar
  31. Paoletti P, Bellone C, Zhou Q (2013) NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci 14:383–400CrossRefPubMedGoogle Scholar
  32. Smith GR (1992) The epidemiology and treatment of depression when it coexists with somatoform disorders, somatization, or pain. Gen Hosp Psychiatry 14:265–272CrossRefPubMedGoogle Scholar
  33. Szewczyk B et al (2010) Decreased expression of Freud-1/CC2D1A, a transcriptional repressor of the 5-HT1A receptor, in the prefrontal cortex of subjects with major depression. Int J neuropsychopharmacol Off Sci J Collegium Int Neuropsychopharmacol 13:1089–1101Google Scholar
  34. Tomaz VS et al (2014) Antidepressant-like effect of nitric oxide synthase inhibitors and sildenafil against lipopolysaccharide-induced depressive-like behavior in mice. Neuroscience 268:236–246CrossRefPubMedGoogle Scholar
  35. Vasquez CE, Riener R, Reynolds E, Britton GB (2014) NMDA receptor dysregulation in chronic state: a possible mechanism underlying depression with BDNF downregulation. Neurochem Int 79:88–97CrossRefPubMedGoogle Scholar
  36. Xu Y et al (2013) Ferulic acid increases pain threshold and ameliorates depression-like behaviors in reserpine-treated mice: behavioral and neurobiological analyses. Metab Brain Dis 28:571–583CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shuo Li
    • 1
  • Jing Han
    • 1
  • Dong-sheng Wang
    • 2
  • Bin Feng
    • 1
  • Ya-ting Deng
    • 1
  • Xin-shang Wang
    • 1
  • Qi Yang
    • 1
  • Ming-gao Zhao
    • 1
  1. 1.Department of Pharmacology, School of PharmacyThe Fourth Military Medical UniversityXi’anChina
  2. 2.Department of Orthopedics, Jinling Hospital, Clinical School of NanjingSecond Military Medical UniversityNanjingChina

Personalised recommendations