• Korean Journal of Pharmacognosy
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• v.17 no.2
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• pp.139-147
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• 1986

Ginseng saponins(GS), protopanaxadiol saponins(PD) and protopanaxatriol saponins (PT) were tested for the inhibition of the development of morphine tolerance and dependence antagonism of morphine analgesia and the loss of morphine tolerance and dependence in mice The results were as follows: 1. Inhibition of the development of morphine tolerance and dependence. 2. Antagonism of morphine analgesia. 3. Increase in the loss of morphine tolerance and dependence. Antagonism of morphine by ginseng saponins and its reversal by L-DOPA and 5-HTP suggest some possibility that catecholamines and serotonin levels might be associated with the results.

• Toxicological Research
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• v.19 no.4
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• pp.311-314
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• 2003

This study was performed to investigate the effects of glycine on the development of tolerance to and physical dependence on morphine. Repeated administration of morphine (10 mg/kg) developed tolerance and physical dependence. Glycine (100, 200 and 400 mg/kg) was administered intraperitoneally (i.p.) to mice for 7 days prior to the morphine injection. Analgesic effects were estimated by the tail flick methods. The inhibitory degree of the development of morphine-induced analgsic tolerance by i.p. administration of glycine was evidenced by the increase in analgesic response to morphine. Glycine inhibited the development of tolerance to morphine. In addition, we separately measured jumping response as the naloxone-precipitated withdrawal sign in mice that had received the same morphine. Glycine reduced the number of jumping behaviors in morphine dependent mice. These results suggest that glycine might be useful the prevention or treatment of morphine tolerance and physical dependence.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.276-282
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• 2002

Morphine has been used widely on the treatment of many types of chronic pain. However the development of tolerance to morphine by repeat application is a major problem in pain therapy. The purpose of the present study was to investigate whether combined administration of nalbuphine with morphine affects the development of tolerance to and dependence on morphine. We hypothesize that the use of nalbuphine, k-agonist may prove to be useful adjunct therapy to prevent morphine-induced undesirable effects in the management of some forms of chronic pain. Morphine (10 mg/kg) was injected to rats intraperitoneally for 5 days. The variable dose of nalbuphine (0.1, 1.0 and 5.0 mg/kg) was administered (i.p.) in combination with morphine injection. The development of tolerance to morphine was assessed by measuring the antinociceptive effect with the Randall-Selitto apparatus. The development of dependence on morphine was determined by the scoring the precipitated withdrawal signs for 20 min after injection of naloxone (10 mg/kg, i.p.). Nalbuphine did not attenuate antinociceptive effect of morphine in rats. Interestingly, combined administration of morphine with nalbuphine (100:1) significantly attenuated the development of morphine tolerance and dependence. These results suggest that the co-administration of nalbuphine with morphine in chronic morphine treatment can be one of therapies to reduce the development of dependence on morphine.

• Archives of Pharmacal Research
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• v.13 no.1
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• pp.38-42
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• 1990

The present study was undertaken to determine the inhibitory effects of cholane compounds, unsodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on the development of morphine-induced tolerance and physical dependence, and also to determine the hepatic glutathione contents. UDCA and CDCA inhibited the development of morphine-induced tolerance and physical dependence significantly. UDCA inhibited the hepatic glutathione decrease induced by morphine multiple injections, while this effect was not observed in CDCA treated mice. It was throught that the inhibitory effects of hepatic glutathione decrease in morphine-treated mice by UDCA and CDCA showed a tendency of inhibitory effects of development of morphine tolerance and dependence.

• Archives of Pharmacal Research
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• v.10 no.3
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• pp.188-192
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• 1987

The present study was undertaken to determine the inhibitory effects of orally administered ginseng saponins (GS), protopanaxadiol saponins (PD), protopanaxatriol saponins (PT) and ginseng ether fraction (GE) on the development of morphine induced tolerance and physical dependence in mice and also to determine the hepatic glutathione contents. GS, PD and PT inhibited significantly the development of morphine induced tolerance and physical dependence, but GE was effective only on the inhibition of the development of morphine induced physical dependence. GS, PD, PT and GE also inhibited the hepatic glutathione level decrease induced by morphine multiple injections.

• Toxicological Research
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• v.11 no.1
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• pp.63-68
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• 1995

N-methyl-D-aspartate(NMDA) receptor has been well known as an important mediator of several forms of neural and behavioral plasticity. But different results were reported about the effect of MK-801 or dextromethorphan on opioid dependence. The present studies examined whether NMDA receptor antagonists can alter the opioid dependence and tolerance in rodents. Naloxone precipitated withdrawal symptoms and changes of locomotor activities were observed in MK-801 or dextromethorphan pretreated morphine-dependent rats. Tail-flick assay was used for morphine analgesia and tolerance was found after 4 day's consecutive injections (10 mg/kg, s.c., twice/day) of morphine in mice. Locomotor activity was increased and the withdrawal symptoms were decreased by the pretreatment of MK-801 in morphine-dependent rats. But 0.3 mg/kg i.p. of MK-801 intensified the body weight loss and produced severe ataxia and rotation although some withdrawal signs were attenuated. Morphine induced analgesic tolerance was inhibited by the pretreatment of MK-801 and dextromethorphan. Dextromethorphan was more potent than MK-801 in inhibiting the development of the analgesic tolerance in mice. These results suggest that NMDA system may be involved in opioid withdrawal and analgesic tolerance but appropriate caution should be requested when MK-801 is used in combination with opioid because of untoward neurologic signs.

• Proceedings of the Ginseng society Conference
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• 1987.06a
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• pp.38-46
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• 1987

The present study was undertaken to determine the inhibitory effects of orally administered ginseng saponins (GS), protopanaxadiol saponins(PD) and protopanaxatriol saponins(PT) on the development of morphine induced tolerance and physical dependence in mice, and to determine the increases in the loss of morphine tolerance and dependence. The study also sought to determine the hepatic glutathione contents, which are closely related to the degree of detoxication of morphinone, a novel metabolite of morphine, and the effects of ginseng saponins on morphine 6-dehydrogenase. The results of the present study showed that GS, PD and PT administered orally inhibited the development of morphine-induced tolerance and dependence. GS, PD and PT, however, increased the loss of morphine tolerance and dependence. GS, PD and PT inhibited the reduction of hepatic glutathione concentration in mice treated chronically with morphine, and the activity of morphine 6-dehydrogenase. So we hypothesized that these results were partially due to the dual action of the test drugs, the inhibition of morphine production and the activation in morphine-glutathione conjugation due to the increased glutathione level for detoxication.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.153.1-153.1
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• 2003

This study was performed to investigate the effects of adenosine on the development of tolerance to and physical dependence on morphine. Repeated adminstration of morphine developed tolerance and physical dependence. Adenosine (1, 2 and 4 mg $kg^{-1}$ i.p.) was administered intraperitoneally to mice for 7 days once a day 30 minutes prior to the morphine (10 mg $kg^{-1}$ s.c.). (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.152.1-152.1
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• 2003

This study was performed to investigate the effects of glycine on the development of tolerance to and physical dependence on morphine. Repeated adminstration of morphine developed tolerance and physical dependence. Glycine (100, 200 and 400 mg $kg^{-1}$ i.p.) was administered intraperitoneally to mice for 7 days once a day 30 minutes prior to the morphine (10 mg $kg^{-1}$ s.c.). (omitted)

• Journal of Ginseng Research
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• v.29 no.2
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• pp.86-93
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• 2005

This study was undertaken to determine the antagonism of the ginseng total saponin (GTS) on the development of nalbuphine-induced tolerance and physical dependence. GTS is blown to have antinarcotic action with a dose of 100mg/kg (i.p.) in rats. STS significantly inhibits the development of nalbuphine-induced physical dependence as well as the tolerance. The level of pCREB was elevated in the striatum by the chronic treatment with nalbuphine or GTS, how-ever, the elevation of pCREB was inhibited by the GTS co-treatment. It has been suggested that NMDA receptor and/or NO is involved in the penomena of opioid dependence and withdrawal. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or GTS on the cortex, hippocampus and striatum in the rat brain. These results suggest that the GTS could be used to ameliorate the nalbuphine tolerance and withdrawal symptoms.