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Cellular and Molecular Neurobiology

, Volume 34, Issue 3, pp 403–408 | Cite as

Piperine Reverses Chronic Unpredictable Mild Stress-Induced Behavioral and Biochemical Alterations in Rats

  • Qing-Qiu Mao
  • Zhen Huang
  • Xiao-Ming Zhong
  • Yan-Fang Xian
  • Siu-Po Ip
Original Research

Abstract

Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair, which was related to the serotonergic system. The present study aimed to examine the behavioral and biochemical effects of piperine in rats exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. In addition, it was found that serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) contents in the hippocampus and frontal cortex were significantly decreased in CUMS-treated rats. Treating the animals with piperine significantly suppressed behavioral and biochemical changes induced by CUMS. The results suggest that piperine produces an antidepressant-like effect in CUMS-treated rats, which is possibly mediated by increasing 5-HT and BDNF contents in selective brain tissues.

Keywords

Antidepressant Brain-derived neurotrophic factor Chronic unpredictable mild stress Serotonin Piperine 

Notes

Acknowledgments

This project was supported by the Zhejiang Provincial Natural Science Foundation of China (Y2110307).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Chonpathompikunlert P, Wattanathorn J, Muchimapura S (2010) Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer’s disease. Food Chem Toxicol 48:798–802CrossRefPubMedGoogle Scholar
  2. Gupta SK, Bansal P, Bhardwaj RK, Velpandian T (2000) Comparative antinociceptive, anti-inflammatory and toxicity profile of nimesulide vs nimesulide and piperine combination. Pharmacol Res 41:657–662CrossRefPubMedGoogle Scholar
  3. Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677–736PubMedCentralPubMedGoogle Scholar
  4. Ibarguen-Vargas Y, Surget A, Vourc’h P, Leman S, Andres CR, Gardier AM, Belzung C (2009) Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress. Behav Brain Res 202:245–251CrossRefPubMedGoogle Scholar
  5. Ivy AS, Rodriguez FG, Garcia C, Chen MJ, Russo-Neustadt AA (2003) Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant. Pharmacol Biochem Behav 75:81–88CrossRefPubMedGoogle Scholar
  6. Juric DM, Miklic S, Carman-Krzan M (2006) Monoaminergic neuronal activity up-regulates BDNF synthesis in cultured neonatal rat astrocytes. Brain Res 1108:54–62CrossRefPubMedGoogle Scholar
  7. Kong LD, Cheng CH, Tan RX (2004) Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones. J Ethnopharmacol 91:351–355CrossRefPubMedGoogle Scholar
  8. Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 2008:894–902CrossRefGoogle Scholar
  9. Lee SA, Hong SS, Han XH, Hwang JS, Oh GJ, Lee KS, Lee MK, Hwang BY, Ro JS (2005) Piperine from the fruits of Piper longum with inhibitory effect on monoamine oxidase and antidepressant-like activity. Chem Pharm Bull 53:832–835CrossRefPubMedGoogle Scholar
  10. Li S, Wang C, Li W, Koike K, Nikaido T, Wang MW (2007a) Antidepressant-like effects of piperine and its derivative, antiepilepsirine. J Asian Nat Prod Res 9:421–430CrossRefPubMedGoogle Scholar
  11. Li S, Wang C, Wang M, Li W, Matsumoto K, Tang Y (2007b) Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. Life Sci 80:1373–1381CrossRefPubMedGoogle Scholar
  12. Mao QQ, Ip SP, Ko KM, Tsai SH, Che CT (2009) Peony glycosides produce antidepressant-like action in mice exposed to chronic unpredictable mild stress: effects on hypothalamic–pituitary–adrenal function and brain-derived neurotrophic factor. Prog Neuropsychopharmacol Biol Psychiatry 33:1211–1216CrossRefPubMedGoogle Scholar
  13. Mao QQ, Huang Z, Zhong XM, Feng CR, Pan AJ, Li ZY, Ip SP, Che CT (2010a) Effects of SYJN, a Chinese herbal formula, on chronic unpredictable stress-induced changes in behavior and brain BDNF in rats. J Ethnopharmacol 128:336–341CrossRefPubMedGoogle Scholar
  14. Mao QQ, Xian YF, Ip SP, Tsai SH, Che CT (2010b) Long-term treatment with peony glycosides reverses chronic unpredictable mild stress-induced depressive-like behavior via increasing expression of neurotrophins in rat brain. Behav Brain Res 210:171–177CrossRefPubMedGoogle Scholar
  15. Mao QQ, Huang Z, Ip SP, Xian YF, Che CT (2011a) Role of 5-HT(1A) and 5-HT(1B) receptors in the antidepressant-like effect of piperine in the forced swim test. Neurosci Lett 504:181–184CrossRefPubMedGoogle Scholar
  16. Mao QQ, Xian YF, Ip SP, Che CT (2011b) Involvement of serotonergic system in the antidepressant-like effect of piperine. Prog Neuropsychopharmacol Biol Psychiatry 35:1144–1147CrossRefPubMedGoogle Scholar
  17. Mao QQ, Huang Z, Ip SP, Xian YF, Che CT (2012) Peony glycosides reverse the effects of corticosterone on behavior and brain BDNF expression in rats. Behav Brain Res 227:305–309CrossRefPubMedGoogle Scholar
  18. Mattson MP, Maudsley S, Martin B (2004) BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 27:589–594CrossRefPubMedGoogle Scholar
  19. Monteggia LM, Luikart B, Barrot M, Theobold D, Malkovska I, Nef S, Parada LF, Nestler EJ (2007) Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biol Psychiatry 61:187–197CrossRefPubMedGoogle Scholar
  20. Porsolt RD, Pichon MLE, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressant. Arch Int Pharmacodyn Ther 229:327–336PubMedGoogle Scholar
  21. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 122:509–522PubMedGoogle Scholar
  22. Selvendiran K, Singh JP, Krishnan KB, Sakthisekaran D (2003) Cytoprotective effect of piperine against benzo[a]pyrene induced lung cancer with reference to lipid peroxidation and antioxidant system in Swiss albino mice. Fitoterapia 74:109–115CrossRefPubMedGoogle Scholar
  23. Tõnissaar M, Mällo T, Eller M, Häidkind R, Kõiv K, Harro J (2008) Rat behavior after chronic variable stress and partial lesioning of 5-HT-ergic neurotransmission: effects of citalopram. Prog Neuropsychopharmacol Biol Psychiatry 32:164–177CrossRefPubMedGoogle Scholar
  24. Willner P (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 134:319–329CrossRefPubMedGoogle Scholar
  25. Willner P (2005) Chronic mild stress (CMS) revisited: consistency and behavioural–neurobiological concordance in the effects of CMS. Neuropsychobiology 52:90–110CrossRefPubMedGoogle Scholar
  26. Zhou J, Li L, Tang S, Cao X, Li Z, Li W, Li C, Zhang X (2008) Effects of serotonin depletion on the hippocampal GR/MR and BDNF expression during the stress adaptation. Behav Brain Res 195:129–138CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Qing-Qiu Mao
    • 1
    • 2
  • Zhen Huang
    • 2
  • Xiao-Ming Zhong
    • 2
  • Yan-Fang Xian
    • 1
  • Siu-Po Ip
    • 1
  1. 1.School of Chinese MedicineThe Chinese University of Hong KongShatinHong Kong
  2. 2.College of PharmacyZhejiang Chinese Medicine UniversityHangzhouChina

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