Browse > Article
http://dx.doi.org/10.4014/jmb.1103.03016

Wild Ginseng Attenuates Repeated Morphine-Induced Behavioral Sensitization in Rats  

Lee, Bom-Bi (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University)
Kwon, Sun-Oh (The Graduate School of Basic Science of Oriental Medicine, College of Oriental Medicine, Kyung Hee University)
Yeom, Mi-Jung (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)
Publication Information
Journal of Microbiology and Biotechnology / v.21, no.7, 2011 , pp. 757-765 More about this Journal
Abstract
Many studies have suggested that the behavioral and reinforcing effects of morphine are induced by hyperactivation of the mesolimbic dopaminergic system, which results in increases in locomotor activity, c-Fos expression in the nucleus accumbens (NAc), and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). In order to investigate the effect of wild ginseng (WG) on treating morphine addiction, we examined the behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. Intraperitioneal injection of WG (100 and 200 mg/kg), 30 min before administration of a daily injection of morphine (40 mg/kg, s.c.), significantly inhibited morphine-induced increases in c-Fos expression in NAc and TH expression in VTA as well as in locomotor activity, as compared with Panax ginseng. It was demonstrated that the inhibitory effect of WG on the behavioral sensitization after repeated exposure to morphine was closely associated with the reduction of dopamine biosynthesis and postsynaptic neuronal activity. It suggests that WG extract may be effective for inhibiting the behavioral effects of morphine by possibly modulating the central dopaminergic system and that WG might be a useful resource to develop an agent for preventing and treating morphine addiction.
Keywords
Morphine; ginseng; locomotor activity; c-Fos; tyrosine hydroxylase; dopamine;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 1  (Related Records In Web of Science)
연도 인용수 순위
1 Cadoni, C. and G. D. Chiara. 1999. Reciprocal changes in dopamine responsiveness in the nucleus accumbens shell and core and in the dorsal caudate-putamen in rats sensitized to morphine. Neuroscience 90: 447-455.   DOI   ScienceOn
2 Curran, E. J., H. Akil, and S. J. Watson. 1996. Psychomotor stimulant and opiate-induced Fos mRNA expression patterns in the rat forebrain: Comparisons between acute drug treatment and a drug challenge in sensitized animals. Neurochem. Res. 21: 1425-1435.   DOI   ScienceOn
3 Devine, D. P. and R. A. Wise. 1994. Self-administration of morphine, DAMGO, and DPDPE into the ventral tegmental area of rats. J. Neurosci. 14: 1978-1984.   DOI
4 Everitt, B. J., A. Dickinson, and T. W. Robbins. 2001. The neuropsychological basis of addictive behavior. Brain Res. Rev. 36: 129-138.   DOI
5 Frankel, P. S., R. E. Harlan, and M. M. Garcia. 1999. Chronic administration of morphine alters immediate-early gene expression in the forebrain of post-dependent rats. Brain Res. 835: 204-212.   DOI   ScienceOn
6 Guo, M., J. H. Wang, J. Y. Yang, D. Zhu, N. J. Xu, G. Pei, C. F. Wu, and X. Li. 2004. Roles of ginsenosides on morphineinduced hyperactivity and rewarding effects in mice. Planta Med. 70: 688-690.   DOI   ScienceOn
7 Johnson, P. I. and T. C. Napier. 2000. Ventral pallidal injections of a mu antagonist block the development of behavioral sensitization to systemic morphine. Synapse 38: 61-70.   DOI   ScienceOn
8 Kim, H. S., J. G. Kang, Y. H. Seong, K. Y. Nam, and K. W. Oh. 1995. Blockade by ginseng total saponin of the development of cocaine induced reverse tolerance and dopamine receptor supersensitivity in mice. Pharmacol. Biochem. Behav. 50: 23-27.   DOI   ScienceOn
9 Alper, R. H., K. T. Demarest, and K. E. Moore. 1980. Morphine differentially alters synthesis and turnover of dopamine in central neuronal systems. J. Neural. Transm. 48: 157-165.   DOI
10 Kim, H. S., C. G. Jang, W. K. Park, K. W. Oh, H. M. Rheu, D. H. Cho, and S. Oh. 1996. Blockade by ginseng total saponin of methamphetamine-induced hyperactivity and conditioned place preference in mice. Gen. Pharmacol. 27: 199-204.   DOI   ScienceOn
11 Kim, H. S. and K. S. Kim. 1999. Inhibitory effects of ginseng total saponin on nicotine-induced hyperactivity, reverse tolerance and dopamine receptor supersensitivity. Behav. Brain Res. 103: 55-61.   DOI   ScienceOn
12 Kim, H. C., E. J. Shin, C. G. Jang, M. K. Lee, J. S. Eun, J. T. Hong, and K. W. Oh. 2005. Pharmacological action of Panax ginseng on the behavioral toxicities induced by psychotropic agents. Arch. Pharm. Res. 28: 995-1001.   DOI
13 Kim, S. E., I. Shim, J. K. Chung, and M. C. Lee. 2006. Effect of ginseng saponins on enhanced dopaminergic transmission and locomotor hyperactivity induced by nicotine. Neuropsychopharmacology 31: 1714-1721.   DOI   ScienceOn
14 Lee, B., C. H. Yang, D. H. Hahm, H. J. Lee, S. M. Han, K. S. Kim, and I. Shim. 2008. Inhibitory effects of ginseng total saponins on behavioral sensitization and dopamine release induced by cocaine. Biol. Pharm. Bull. 31: 436-441.   DOI   ScienceOn
15 Kuribara, H. 1995. Modification of morphine sensitization by opioid and dopamine receptor antagonists: Evaluation by studying ambulation in mice. Eur. J. Pharmacol. 275: 251-258.   DOI   ScienceOn
16 Lee, B., S. M. Han, and I. Shim. 2009. Acupuncture attenuates cocaine-induced expression of behavioral sensitization in rats: Possible involvement of the dopaminergic system in the ventral tegmental area. Neurosci. Lett. 449: 128-132.   DOI   ScienceOn
17 Lee, B., J. Park, S. Kwon, M. W. Park, S. M. Oh, M. J. Yeom, I. Shim, H. J. Lee, and D. H. Hahm. 2010. Effect of wild ginseng on scopolamine-induced acetylcholine depletion in the rat hippocampus. J. Pharm. Pharmacol. 62: 263-271.   DOI   ScienceOn
18 Orzi, F., F. Passarelli, M. L. Riccia, R. D. Grezia, and F. E. Pontieri. 1996. Intravenous morphine increases glucose utilization in the shell of the rat nucleus accumbens. Eur. J. Pharmacol. 302: 49-51.   DOI
19 Martin, T. J., M. Miller Jr., S. I. Dworkin, J. E. Smith, and L. J. Porrino. 1997. Alteration of local cerebral glucose utilization following intravenous administration of heroin in Fisher 344 rats. Brain Res. 755: 313-318.   DOI   ScienceOn
20 Nabata, H., H. Saito, and K. Takagi. 1973. Pharmacological studies of neutral saponins (GNS) of Panax ginseng root. Jpn. J. Pharmacol. 23: 29-41.   DOI
21 Paxinos, G. and C. Watson. 1986. The Rat Brain in Stereotaxic Coordinates. New York, Academic Press.
22 Young, S. T., L. J. Porrino, and M. J. Iadarola. 1991. Cocaine induces striatal c-fos-immunoreactive proteins via dopaminergic D1 receptors. Proc. Natl. Acad. Sci. USA 88: 1291-1295.   DOI   ScienceOn
23 Pecins-Thompson, M. and J. Peris. 1993. Behavioral and neurochemical changes caused by repeated ethanol and cocaine administration. Psychopharmacology (Berl.) 110: 443-450.   DOI
24 Phillips, T. J., A. J. Roberts, and C. N. Lessov. 1997. Behavioral sensitization to ethanol: Genetics and the effects of stress. Pharmacol. Biochem. Behav. 57: 487-493.   DOI   ScienceOn
25 Pontieri, F. E., G. Tanda, and G. D. Chiara. 1995. Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the 'shell' as compared to the 'core' of the rat nucleus accumbens. Proc. Natl. Acad. Sci. USA 92: 12304-12308.   DOI   ScienceOn
26 Serrano, A., M. A. Aguilar, C. Manzanedo, M. Rodriguez- Arias, and J. Minarro. 2002. Effects of DA D1 and D2 antagonists on the sensitization to the motor effects of morphine in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 26: 263-271.
27 Shim, I., J. I. Javaid, D. Wirtshafter, S. Y. Jang, K. H. Shin, H. J. Lee, Y. C. Chung, and B. G. Chun. 2001. Nicotine-induced behavioral sensitization is associated with extracellular dopamine release and expression of c-Fos in the striatum and nucleus accumbens of the rat. Behav. Brain Res. 121: 137-147.   DOI   ScienceOn
28 Weissenborn, R., V. Deroche, G. F. Koob, and F. Weiss. 1966. Effects of dopamine agonists and antagonists on cocaineinduced operant responding for a cocaine-associated stimulus. Psychopharmacology (Berl.) 126: 311-322.
29 Yoon, S. S., B. H. Lee, H. S. Kim, K. H. Choi, J. Yun, E. Y. Jang, et al. 2007. Potential roles of GABA receptors in morphine self-administration in rats. Neurosci. Lett. 428: 33-37.   DOI   ScienceOn
30 Zernig, G., I. A. O'Laughlin, and H. C Fibiger. 1997. Nicotine and heroin augment cocaine-induced dopamine overflow in nucleus accumbens. Eur. J. Pharmacol. 337: 1-10.   DOI   ScienceOn
31 Takahashi, E., K. Kudo, K. Harada, T. Kashimoto, Y. Miyate, A. Kakizahi, and E. Takahashi. 1999. Effects of ginseng saponins on responses induced by various receptor stimuli. Eur. J. Pharmacol. 369: 23-32.   DOI   ScienceOn
32 Stewart, J. 1983. Conditioned and unconditioned drug effects in relapse to opiate and stimulant drug self-administration. Prog. Neuropsychopharmacol. Biol. Psychiatry 7: 591-597.   DOI   ScienceOn
33 Stewart, J. 1983. Conditioned and unconditioned drug effects in relapse to opiate and stimulant drug self-administration. Prog. Neuropsychopharmacol. Biol. Psychiatry 7: 591-597.   DOI   ScienceOn
34 Tachikawa, E., K. Kudo, M. Nunokawa, T. Kashimoto, E. Takahashi, and S. Kitagawa. 2001. Characterization of ginseng saponin ginsenoside-Rg(3) inhibition of catecholamine secretion in bovine adrenal chromaffin cells. Biochem. Pharmacol. 62: 943-951.   DOI   ScienceOn
35 Tanda, G., F. E. Pontieri, and G. D. Chiara. 1997. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science 276: 2048-2050.   DOI
36 Taracha, E., S. J. Chrapusta, M. Lehner, A. Skorzewska, P. Maciejak, J. Szyndler, and A. Plaznik. 2008. Morphine and methadone pre-exposures differently modify brain regional Fos protein expression and locomotor activity responses to morphine challenge in the rat. Drug Alcohol Depend. 97: 21-32.   DOI
37 Tokuyama, S., K. W. Oh, H. S. Kim, M. Takahashi, and H. Kaneto. 1992. Blockade by ginseng extract of the development of reverse tolerance to the ambulation-accelerating effect of methamphetamine in mice. Japan J. Pharmacol. 59: 423-425.   DOI
38 Vanderschuren, L. J. and P. W. Kalivas. 2000. Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: A critical review of preclinical studies. Psychopharmacology (Berl.) 151: 99-120.   DOI
39 Uslaner, J., A. Badiani, C. S. Norton, H. E. Day, S. J. Watson, H. Akil, and T. E. Robinson. 2001. Amphetamine and cocaine induce different patterns of c-fos mRNA expression in the striatum and subthalamic nucleus depending on environmental context. Eur. J. Neurosci. 13: 1977-1983.   DOI   ScienceOn
40 van Ree, J. M., M. A. Gerrits, and L. J. Vanderschuren. 1999. Opioids, reward and addiction: An encounter of biology, psychology and medicine. Pharmacol. Rev. 51: 341-396.
41 Vezina, P., P. W. Kalivas, and J. Stewart. 1987. Sensitization occurs to the locomotor effects of morphine and the specific mu-opioid receptor agonist, DAGO, administered repeatedly to the ventral tegmental area but not to the nucleus accumbens. Brain Res. 4: 51-58.
42 Vries, D. T. J., A. N. Schoffelmeer, R. Binnekade, A. H. Mulder, and L. J. Vanderschuren. 1998. Drug-induced reinstatement of heroin- and cocaine-seeking behavior following long-term extinction is associated with expression of behavioral sensitization. Eur. J. Neurosci. 10: 3565-3571.   DOI   ScienceOn