Cellular and Molecular Neurobiology

, Volume 28, Issue 5, pp 745–755 | Cite as

Effects of the Chinese Traditional Prescription Xiaoyaosan Decoction on Chronic Immobilization Stress-induced Changes in Behavior and Brain BDNF, TrkB, and NT-3 in Rats

Original Paper


The Xiaoyaosan (XYS) decoction, a Chinese traditional prescription containing eight commonly used herbs, has been used for treatment of mental disorders such as depression for centuries in China. However, the mechanism underlying its antidepressant activity is poorly understood. In rats with chronic immobilization stress (CIS), we examined the effects of the XYS decoction on tail suspension behavior and the levels of brain-derived neurotrophic factor (BDNF), tyroxine hydroxylase (TrkB), and neurotrophin 3 (NT-3) in the frontal cortex and hippocampus. Rats subjected to CIS exhibited decreases in weight-gain, food intake, and ambulation in the open field test; they also showed an increase in immobility in the tail suspension test. These were all attenuated by the XYS decoction. Biochemically, the XYS decoction also reversed CIS-induced decreases in BDNF and increases in TrkB and NT-3 in the frontal cortex and the hippocampal CA1 subregion. The behavioral effects of the XYS were correlated to the biochemical actions. These results suggest that the XYS decoction produces an antidepressant-like effect, which appears to be involved by BDNF in the brain.


Repeated immobilization stress Xiaoyaosan decoction BDNF TrkB NT-3 Traditional Chinese medicine 


  1. Altemus KL, Lavenex P, Ishizuka N, Amaral DG (2005) Morphological characteristics and electrophysiological properties of CA1 pyramidal neurons in macaque monkeys. Neuroscience 136:741–756PubMedCrossRefGoogle Scholar
  2. Amelia RN, Tony H, Ronald R, Patrick K, Russo N (2001) Physical activity—antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model. Behav Brain Res 120:87–95CrossRefGoogle Scholar
  3. Bachmann RF, Schloesser RJ, Gould TD, Manji HK (2005) Mood stabilizers target cellular plasticity and resilience cascades: implications for the development of novel therapeutics. Mol Neurobiol 32:173–202PubMedCrossRefGoogle Scholar
  4. Bartoletti A, Cancedda L, Reid SW, Tessarollo L, Porciatti V, Pizzorusso T, Maffei L (2002) Heterozygous knock-out mice for brain-derived neurotrophic factor show a pathway-specific impairment of long-term potentiation but normal critical period for monocular deprivation. J Neurosci 22:10072–10077PubMedGoogle Scholar
  5. Chen FK, Meng XS, Guo YZ, Kano Y (1992) The identification and determination of marker substances in xiaoyao wan by three dimensional HPLC. Yao Xue Xue Bao 27:853–857PubMedGoogle Scholar
  6. Chen JX, Li W, Zhao X, Yang JX, Xu HY, Wang ZF, Yue GX (2004) Changes of mRNA expression of enkephalin and prodynorphin in hippocampus of rats with chronic immobilization stress. World J Gastroenterol 10:2547–2549PubMedGoogle Scholar
  7. Chen JX, Ji B, Lu ZL, Hu LS (2005a) Effects of chai hu (Radix Burpleuri) containing formulation on plasma β-endorphin, epinephrine and dopamine in patients. Am J Chin Med 33:737–745PubMedCrossRefGoogle Scholar
  8. Chen J, Zhao X, Yue G, Xu H (2005b) Changes of CRF, POMC, ENK, Pro-DYN, BDNF, and NT3 in rat brain response to chronic immobilization stress: with effects of Chinese herbs. 2005 Abstract Viewer/Itinerary Planner. Society for Neuroscience, Washington, DC, OnlineGoogle Scholar
  9. Conover JC, Erickson JT, Katz DM, Bianchi LM, Poueymirou WT, McClain J, Pan L, Helgren M, Ip NY, Boland P et al (1995) Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 375:235–238PubMedCrossRefGoogle Scholar
  10. Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606PubMedGoogle Scholar
  11. Fujioka T, Fujioka A, Endoh H, Sakata Y, Furukawa S, Nakamura S (2002) Materno-fetal coordination of stress-induced Fos expression in the hypothalamic paraventricular nucleus during pregnancy. Neuroscience 118:409–415CrossRefGoogle Scholar
  12. Fumagalli F, Racagni G, Colombo E, Riva MA (2003) BDNF gene expression is reduced in the frontal cortex of dopamine transporter knockout mice. Mol Psychiatry 8:898–899PubMedCrossRefGoogle Scholar
  13. Jang MH, Shin MC, Lim BV, Chung JH, Kang HS, Kang SA, Choue RW, Kim EH, Kim CJ (2002) Nicotine administration decreases nitric oxide synthase expression in the hypothalamus of food deprived rats. Neurosci Lett 322:29–32PubMedCrossRefGoogle Scholar
  14. Kim J, Yoon K (1998) Stress: metaplastic effects in the hippocampus. Trends Neurosci 21:505–509PubMedCrossRefGoogle Scholar
  15. Kuroda Y, McEwen BS (1998) Effect of chronic restraint stress and tianeptine on growth factors, growth-associated protein-43 and microtubule-associated protein 2 mRNA expression in the rat hippocampus. Brain Res. Mol Brain Res 59:35–39PubMedCrossRefGoogle Scholar
  16. Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS (1994) Neurotrophic factors: from molecule to man. Trends Neurosci 17:182–190PubMedCrossRefGoogle Scholar
  17. Maroun M, Richter-Levin G (2003) Exposure to acute stress blocks the induction of long-term potentiation of the amygdala-prefrontal cortex pathway in vivo. J Neurosci 23:4406–4409PubMedGoogle Scholar
  18. McEwen BS (2005) Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54(5 Suppl 1):20–23PubMedCrossRefGoogle Scholar
  19. Nibuya M, Takahashi M, Russell DS, Duman RS (1999) Repeated stress increases catalytic TrkB mRNA in rat hippocampus. Neurosci Lett 267:81–84PubMedCrossRefGoogle Scholar
  20. Pang PT, Lu B (2004) Regulation of late-phase LTP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF. Ageing Res Rev 3:407–430PubMedCrossRefGoogle Scholar
  21. Pezawas L, Verchinski BA, Mattay VS, Callicott JH, Kolachana BS, Straub RE, Egan MF, eyer-Lindenberg A, Weinberger DR (2004) The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci 24:10099–10102PubMedCrossRefGoogle Scholar
  22. Qin XS, Jin KH, Ding BK, Xie SF, Ma H (2005) Effects of extract of Ginkgo biloba with venlafaxine on brain injury in a rat model of depression. Chin Med J (Engl) 118:391–397Google Scholar
  23. Rage F, Givalois L, Marmigere F, Tapia-Arancibia L, Arancibia S (2002) Immobilization stress rapidly modulates BDNF mRNA expression in the hypothalamus of adult male rats. Neurosci 112:309–318CrossRefGoogle Scholar
  24. Siuciak JA, Lewis DR, Wiegand SJ, Lindsay RM (1997) Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav 56:131–137PubMedCrossRefGoogle Scholar
  25. Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15(3 Pt 1):1768–1777PubMedGoogle Scholar
  26. Xu H, Qing H, Lu W, Keegan D, Richardson JS, Chlan-Fourney J, Li XM (2002) Quetiapine attenuates the immobilization stress-induced decrease of brain-derived neurotrophic factor expression in rat hippocampus. Neurosci Lett 321:65–68PubMedCrossRefGoogle Scholar
  27. Yun SJ, Park HJ, Yeom MJ, Hahm DH, Lee HJ, Lee EH (2002) Effect of electroacupuncture on the stress-induced changes in brain-derived neurotrophic factor expression in rat hippocampus. Neurosci Lett 318:85–88PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.School of Pre-clinical MedicineBeijing University of Traditional Chinese MedicineBeijingP. R. China

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