• 생약학회지
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• 제20권2호
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• pp.123-127
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• 1989

The effects of ginsenosides on the development of morphine induced tolerance and physical dependence were investigated. $Rb_1,\;Rb_2,\;Rg_1\;and\;Re$ inhibited significantly the development of morphine induced tolerance but $Rb_1\;and\;Rg_1$ showed significant inhibitory effect on the naloxone induced withdrawal jumping response. Ginsenosides inhibited the body weight decrease in physically dependent mice during multiple injection of morphine.

• Journal of Ginseng Research
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• 제32권1호
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• pp.1-7
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• 2008

Ginseng saponin has been shown to inhibit the development of dependence on morphine, cocaine, methamphetamine, but the antinarcotics effects of ginseng on nalbuphine remains still largely unknown. Ginseng administration attenuated the naloxone-induced jumping behavior on nalbuphine dependent mice. The development of morphine dependence was mediated through ${\mu}-opioid$ receptor, however, development of nalbuphine dependence was mediated through ${\kappa}-opioid$ receptor. However, it was found that the efficacy of analgesic antagonism of GTS was mediated through the serotonergic mechanism, not mediated through the opioid receptor. In addition, ginseng administration modulated cellular signal transduction in the brain. The increased NMDA receptor subunit (NR1, pNR1), phosphate extracellular signal regulated protein kinase (pERK), phosphate cAMP response element binding protein (pCREB) expression by nalbuphine was decreased by the administration of ginseng powder in cortex, hippocampus, striatum of rat brain. These results suggest that ginseng could be one of the targets of antinarcotic therapies to reduce the development of tolerance and dependence on nalbuphine as well as morphine.

• Archives of Pharmacal Research
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• 제26권7호
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• pp.540-544
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• 2003

Morphine, an analgesic with significant abuse potential, is considered addictive because of drug craving and psychological dependence. It is reported that repeated treatment of morphine can produce conditioned place preference (CPP) showing a reinforcing effect in mice. CPP is a useful method for the screening of morphine-induced psychological dependence. In the present study, we investigated the effect of the methanolic extract of Coptis japonica (MCJ) on morphine-induced CPP in mice. Furthermore, we examined c-fos expression in the parietal cortex, piriform cortex, striatum, nucleus accumbens, and hippocampus of the morphine-induced CPP mouse brain. Treatment of MCJ 100 mg/kg inhibited morphine-induced CPP. Expression of c-fos was increased in the cortex, striatum, nucleus accumbens, and hippocampus of the morphine-induced CPP mouse brain. These increases of expression were inhibited by treatment with MCJ 100 mg/kg, compared to the morphine control group. Taken together, these results suggest that MCJ inhibits morphine-induced CPP through the regulation of c-fos expression in the mouse brain.

• Journal of Ginseng Research
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• 제23권4호
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• pp.239-246
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• 1999

백서를 이용하여 진세노사이드 흑은 모르핀을 척수강내 투여한 다음 tail-flick test를 통하여 진통 작용을 연구하였다. 또한, 진세노사이드를 모르핀과 함께 척수강내 장기 처리할 경우 모르핀에 의한 내성 및 의존성 유발에 미치는 영향을 연구하였다. 연구 결과, 척수강내 진세노사이드의 투여는 200 ${\mu}g$/rat에서 약한 진통 작용이 있는 것으로 나타났다. 모르핀은 투여 농도에 의존적으로 좋은 진통 효능을 보여주었으며, $ED_50$은 1.2 ${\mu}g/rat$인 것으로 나타났다. 그러나 진세노사이드의 모르핀을 함께 척수강내 투여할 경우 모르핀의 진통 작용을 증가 시키지 않은 것으로 나타났다. 200 ug/rat 진세노사이드를 10 ${\mu}g$/rat모르핀을 7일 동안 같이 투여할 경우 모르핀에 의한 통증 작용에 대한 내성을 억제하였으며, 모르핀에 의한 의존성을 부분적으로 억제하는 것으로 나타났다. 이러한 연구 결과는 척수 수준에서 진세노사이드가 모르핀의 장기 투여에 의하여 유도되는 모르핀에 대한 내성 및 의존성을 억제하는 것으로 사료된다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1988년도 학술대회지
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• pp.151-155
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• 1988

인삼사포닌, 프로토파낙사다이옥 사포닌 및 푸로토파낙사트리올 사포닌의 몰핀내성 및 의존성 형성억제 작용을 연구하였다. 인삼사포닌은 독성이 10배, 진통력은 1/2인 morphinone으로 대사시키는 morphine 6-hydrogenase의 작용을 억제시켜 morphinone의 생성을 증가시켜 morphine glutathione conjugation을 촉진시키므로 morphinone의 해독작용이 증가된다. 또한 인삼은 척수하행성 억제계의 활성을 억제하여 몰핀의 진통력을 길항하므로 신경계 기능상의 변화도 몰핀의 내성 및 의존성형성 억제작용에 관여하는 것으로 추정된다.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.113-117
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• 2008

Morphine is a potent analgesic with significant abuse potential, because of drug craving and psychological dependence. It is reported that repeated treatment of morphine can produce conditioned place preference (CPP) showing a reinforcing effect in mice. Previously, we have reported the inhibitory effect of the methanolic extract of Coptis japonica (MCJ) on morphine-induced CPP in mice. The present study was employed whether p-CREB expression is involved in the inhibitory effect of MCJ on the morphine-induced CPP in the mouse hippocampus. Repeated administration of MCJ 100 mg/kg inhibited morphine-induced CPP. Expression of p-CREB was increased in the dentate gyrus of the hippocampus that had undergone morphineinduced CPP. This increase of expression was significantly inhibited by administration of MCJ 100 mg/kg, compared to the morphine control group. Taken together, these results suggest that MCJ inhibits morphine-induced CPP through the regulation of p-CREB expression in the mouse dentate gyrus of the hippocampus.

• Journal of Ginseng Research
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• 제11권2호
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• pp.123-129
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• 1987

Antagonisms of the analgesic effect of morphine in mice by ginsenoside Rbl, Rb2, Rgl and Re were investigated in these experiments. These ginsenosides antagonized the analgesic effect induced by morphine in mice and the administration of 2,4-dihy-droxyphenylalanine or 5-hydroxytryptophan reduced the antagonisms of morphine analgesia by the ginsenosides. Possible mechanisms involved in the antagonistic actions of the ginsenosides on morphine analgesia were described.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-1
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• pp.112-112
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• 2003

Morphine is a potent analgesic and addictive substance. Morphine produces neurotoxicity such as rewarding effect, analgesic tolerance and physical dependence. It has been restricted to the use of morphine in patients because of these problems. The present study was investigated the effect of berberine on the neurotoxicity of morphine. Repeated administration of morphine produced conditioned place prefernece (CPP) and behavioral sensitization in mice. (omitted)

• Journal of Ginseng Research
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• 제14권2호
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• pp.178-186
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• 1990

The analgesic effect of morphine was antagonized and the development of tolerance was suppressed by the modification of the neurologic function in the animals treated with ginseng saponins The activation of the spinal descending inhibitory systems as well as the supraspinal structures by the administration of morphine was inhibited in the animals treated with ginseng saponine intracerebrally or intrathecally. The development of morphine tolerance and dependence, and the abrupt expression of naloxone inducted abstinence syndrom were also inhibited by ginsenoside Rb1, Rb2, Rg1 and Re. These results suggest that ginsenoside Rbl, Hbs, Rgl and Re are the bioactive components of panax ginseng on the inhibition of the development of morphine tolerance and dependence, and the inhibition of abrupt abstinence sindrome. In addition, further research on the minor components of Pnnnxkinsenl should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain in level of monoamines at the variolls time intervals and at the various day intervals, respectively. The inhibitory or facilitated effects of ginseng saponins on electrically evoked contractions in guinea pig ileum ($\mu$-receptor) and mouse vats deferens ($\delta$-receptor) were not mediated through opioid receptors. The antagonism of a $\chi$ receptor agonist, U-50, 488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, but mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine 6-dehydrogenase which catalyzed the production of morphinone from morphine, and increased hepatic glutathione contents for the detoxication of morphinone. This result suggests that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and dependence.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2005년도 창립30주년기념 추계 학술대회 및 정기총회
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• pp.41-63
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• 2005

Ginseng has been useful for the treatment of diverse disease in oriental countries for thousands of years. In addition, a folk medicine prescribed by seven herbal drugs including Panax ginseng has been antinarcotics in the treatment of morphine-dependent patients. Many articles have been reported on these works. Therefore, we review the protective effects of Panax ginseng on the neurotoxicity induced by abuse drugs. Ginseng total saponins (GTS) extracted and isolated by Panax ginseng antagonized morphine-induced analgesia, and inhibited the development of analgesic tolerance to and physical dependence on morphine. CTS inhibited morphine-6 dehydrogenase, which catalyzes production of mophinone from morphine, and increased hepatic glutathione level responsible to toxicity. Therefore, wehypothesized that these dual actions of ginseng can be associated with the detoxication of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contraction in guinea pig ileum (${\mu}$-receptors) and mouse vas deferens(${\delta}$-receptors) were not mediated through opioid receptors, suggesting non-opioid mechanisms. On the hand, antagonism of U-50,488H (${\kappa}$-agonist)-induced antinociception is mediated by serotonergic mechanisms. GTS also inhibited hyperactivity, reverse tolerance (sensitization) and conditioned place preference-induced by psychostimulants such as methamphetamine, cocaine and morphine. On the other hand, GTS reduced the dopamine levels induced by methamphetamine. Moreover, GTS blocked the development of dopamine receptor activation, showing antidopaminergic effect. We suggest that GTS prevent the methamphetamine-induced striatal dopaminergic neurotoxicity. In addition, Ginsenoside also attenuates morphine-induced CAMP signaling pathway. These results suggested that GTS might be useful for the therapy of the adverse actions of drugs with abuse liability.