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Wild Ginseng Attenuates Anxiety- and Depression-Like Behaviors During Morphine Withdrawal

  • Lee, Bom-Bi (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University) ;
  • Kim, Hyuk (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University) ;
  • Shim, In-Sop (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University) ;
  • Lee, Hye-Jung (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University) ;
  • Hahm, Dae-Hyun (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University)
  • Received : 2011.06.13
  • Accepted : 2011.07.13
  • Published : 2011.10.28

Abstract

The purpose of this study was to evaluate whether wild ginseng (WG) administration could attenuate anxiety- and depression-like behaviors and expression of corticotrophin-releasing factor (CRF) and neuropeptide Y (NPY) following withdrawal from repeated morphine administration in rats. Male rats were administered daily doses of WG (50, 100, or 200 mg/kg, i.p.) for 5 days, 30 min before morphine injection (40 mg/kg, s.c). The anxiety- and depression-like behavioral responses were measured 72 h after the last morphine injection using an elevated plus maze (EPM) and forced swimming test (FST), respectively. Changes in hypothalamic CRF and NPY expressions were also examined by analyzing their immunoreactivities in the hypothalamus. Daily administration of WG significantly reduced anxiety- and depression-like behavior, and elicited the suppression of CRF expression and the stimulation of NPY expression in the hypothalamus. Our results demonstrated that WG extract might be effective at inhibiting the anxiety and depression responses due to morphine withdrawal by possibly modulating the hypothalamus CRF and NPY systems. Furthermore, these findings imply that WG extract can be used for developing new medication to cure or alleviate morphine withdrawal symptoms and to prevent relapses of morphine use.

Acknowledgement

Supported by : Kyung Hee University

References

  1. Anraku, T., Y. Ikegaya, N. Matsuki, and N. Nishiyama. 2001. Withdrawal from chronic morphine administration causes prolonged enhancement of immobility in rat forced swimming test. Psychopharmacology (Berl). 157: 217-220. https://doi.org/10.1007/s002130100793
  2. Chatterjee, M., P. Verma, and G. Palit. 2010. Comparative evaluation of Bacopa monniera and Panax quniquefolium in experimental anxiety and depressive models in mice. Indian J. Exp. Biol. 48: 306-313.
  3. Coventry, T. L., D. S. Jessop, D. P. Finn, M. D. Crabb, H. Kinoshita, and M. S. Harbuz. 2001. Endomorphins and activation of the hypothalamo-pituitary-adrenal axis. J. Endocrinol. 169: 185-193. https://doi.org/10.1677/joe.0.1690185
  4. Dang, H., Y. Chen, X. Liu, Q. Wang, L. Wang, W. Jia, and Y. Wang. 2009. Antidepressant effects of ginseng total saponins in the forced swimming test and chronic mild stress models of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry 33: 1417-1424. https://doi.org/10.1016/j.pnpbp.2009.07.020
  5. Hodgson, S. R., R. S. Hofford, C. J. Norris, and S. Eitan. 2008. Increased elevated plus maze open-arm time in mice during naloxone-precipitated morphine withdrawal. Behav. Pharmacol. 19: 805-811. https://doi.org/10.1097/FBP.0b013e32831c3b57
  6. Holmes, P. V., A. de Bartolomeis, V. Koprivica, and J. N. Crawley. 1995. Lack of effect of chronic morphine treatment and naloxone-precipitated withdrawal on tyrosine hydroxylase, galanin, and neuropeptide Y mRNA levels in the rat locus coeruleus. Synapse 19: 197-205. https://doi.org/10.1002/syn.890190307
  7. Houshyar, H., F. Gomez, S. Manalo, A. Bhargava, and M. F. Dallman. 2003. Intermittent morphine administration induces dependence and is a chronic stressor in rats. Neuropsychopharmacology 28: 1960-1972. https://doi.org/10.1038/sj.npp.1300271
  8. Langworth, S., O. Bodlund, and H. Agren. 2006. Efficacy and tolerability of reboxetine compared with citalopram: A double-blind study in patients with major depressive disorder. J. Clin. Psychopharmacol. 26: 121-127. https://doi.org/10.1097/01.jcp.0000204138.20417.c3
  9. Lee, B., J. Park, S. Kwon, M. W. Park, S. M. Oh, M. J. Yeom, et al. 2010. Effect of wild ginseng on scopolamine-induced acetylcholine depletion in the rat hippocampus. J. Pharm. Pharmacol. 62: 263-271. https://doi.org/10.1211/jpp.62.02.0015
  10. Lee, B., I. Shim, H. J. Lee, Y. Yang, and D. H. Hahm. 2009. Effects of acupuncture on chronic corticosterone-induced depression-like behavior and expression of neuropeptide Y in the rats. Neurosci. Lett. 453: 151-156. https://doi.org/10.1016/j.neulet.2009.01.076
  11. Lima, C. S., A. Ribeiro-Carvalho, C. C. Filgueiras, A. C. Manhães, A. Meyer, and Y. Abreu-Villaca. 2009. Exposure to methamidophos at adulthood elicits depressive-like behavior in mice. Neurotoxicology 30: 471-478. https://doi.org/10.1016/j.neuro.2009.01.009
  12. Maric, T., S. Tobin, T. Quinn, and U. Shalev. 2008. Food depression-like effects of neuropeptide Y on heroin self-administration and reinstatement of heroin seeking in rats. Behav. Brain Res. 194: 39-43. https://doi.org/10.1016/j.bbr.2008.06.023
  13. Nabata, H., H. Saito, and K. Takagi. 1973. Pharmacological studies of neutral saponins (GNS) of Panax Ginseng root. Jpn. J. Pharmacol. 23: 29-41. https://doi.org/10.1254/jjp.23.29
  14. Navarro-Zaragoza, J., C. Nunez, J. Ruiz-Medina, M. L. Laorden, O. Valverde, and M. V. Milanes. 2011. $CRF_2$ mediates the increased noradrenergic activity in the hypothalamic paraventricular nucleus and the negative state of morphine withdrawal in rats. Br. J. Pharmacol. 162: 851-862. https://doi.org/10.1111/j.1476-5381.2010.01090.x
  15. Padovan, C. M. and F. S. Guimaraes. 2000. Restraint-induced hypoactivity in an elevated plus-maze. Braz. J. Med. Biol. Res. 33: 79-83.
  16. Papaleo, F., S. Ghozland, M. Ingallinesi, A. J. Roberts, G. F. Koob, and A. Contarino. 2008. Disruption of the CRF(2) receptor pathway decreases the somatic expression of opiate withdrawal. Neuropsychopharmacology 33: 2878-2887. https://doi.org/10.1038/npp.2008.8
  17. Paxinos, G. and C. Watson. 1986. The Rat Brain in Stereotaxic Coordinates. New York, Academic Press.
  18. Pellow, S., P. Chopin, S. E. File, and M. Briley. 1985. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Methods 14: 149-167. https://doi.org/10.1016/0165-0270(85)90031-7
  19. Porsolt, R. D., G. Anton, N. Blavet, and M. Jalfre. 1978. Behavioral despair in rats: A new model sensitive to antidepressant treatments. Eur. J. Pharmacol. 15: 379-391.
  20. Powell, J. E. and D. Taylor. 1992. Anger, depression, and anxiety following heroin withdrawal. Int. J. Addict. 27: 25-35.
  21. Rezayof, A., S. S. Hosseini, and M. R. Zarrindast. 2009. Effects of morphine on rat behaviour in the elevated plus maze: The role of central amygdala dopamine receptors. Behav. Brain Res. 202: 171-178. https://doi.org/10.1016/j.bbr.2009.03.030
  22. Rodgers, R. J. and A. Dalvi. 1997. Anxiety, defence and the elevated plus-maze. Neurosci. Biobehav. 21: 801-810. https://doi.org/10.1016/S0149-7634(96)00058-9
  23. Sarnyai, Z., Y. Shaham, and S. C. Heinrichs. 2001. The role of corticotropin-releasing factor in drug addiction. Pharmacol. Rev. 53: 209-243.
  24. Shi, J., S. X. Li, X. L. Zhang, X. Wang, L. B. Foll, X. Y. Zhang, et al. 2009. Time-dependent neuroendocrine alterations and drug craving during the first month of abstinence in heroin addicts. Am. J. Drug Alcohol Abuse 35: 267-272. https://doi.org/10.1080/00952990902933878
  25. Slawecki, C. J., A. K. Thorsell, A. El Khoury, A. A. Mathe, and C. L. Ehlers. 2005. Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence: Relation to anxiety-like and depressive-like behavior. Neuropeptides 39: 369-377. https://doi.org/10.1016/j.npep.2005.06.002
  26. Tian, M., R. R. Mao, L. P. Wang, Q. X. Zhou, J. Cao, and L. Xu. 2011. Interaction between behavioral despair and addictive behaviors in rats. Physiol. Behav. 102: 7-12. https://doi.org/10.1016/j.physbeh.2010.10.002
  27. Wang, J., S. Flaisher-Grinberg, S. Li, H. Liu, L. Sun, Y. Zhou, and H. Einat. 2010. Antidepressant-like effects of the active acidic polysaccharide portion of ginseng in mice. J. Ethnopharmacol. 132: 65-69. https://doi.org/10.1016/j.jep.2010.07.042
  28. Zomkowski, A. D., A. R. Santos, and A. L. Rodrigues. 2005. Evidence for the involvement of the opioid system in the agmatine antidepressant-like effect in the forced swimming test. Neurosci. Lett. 381: 279-283 https://doi.org/10.1016/j.neulet.2005.02.026