• Journal of Ginseng Research
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• v.19 no.3
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• pp.219-224
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• 1995

The modulatory effects of total ginseng saponin (TGS) on the 1, 6, and opioid receptor binding in morphine tolerance and dependence were examined in this study. The specific [$^{3}H$]DAGO ([D-$Ala^2$, N-$Mephe^4$, $Glyco^4$] enkephalin) binding was significantly increased in chronic morphine (10 mg/kg, i.p.) treated mouse striatum. The specific [$^{3}H$]DPDPE ([D-$Pen^2$, D-$Pen^5$] enkephalin) binding was ignificantly increased following morphine treatment in the mouse striatum and cortex. Also, an apparent decrease in the affinity of [$^{3}H$]DPN (diprenorphine) was observed after chronic morphine treatment in mouse striatum and cortex. 7GS produced a sleight increase of specific [$^{3}H$]DAGO, [$^{3}H$]DPDPE binding and a significant increase of specific [$^{3}H$]DPN binding in the mouse brain striatum. In cortex, TGS produced an inhibition of specific [$^{3}H$]DAGO and [$^{3}H$]DPDPE binding and increase of the specific [$^{3}H$]DPN binding. The prolonged administration of TGS (25, 50, 100, and 150 mg/kg, i.p., 3 wks) produced an inhibition of increased [$^{3}H$]DAGO specific binding following morphine without significant changes in the agonist binding to and receptors in mouse striatum and cortex. These contracted alterations in $\mu$, $\gamma$ and $\kappa$ opiate receptor binding were dependent in TGS dogs and brain sites.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.198-201
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• 2004

This review focuses on finding neurochemical changes in physical dependence on butorphanol, a relatively potent mixed agonist-antagonist opioid analgesic agent that is five times more potent than morphine in antinociceptive effects. The chronic administration of butorphanol induces physical dependence. Withdrawal from such dependence can be reliably precipitated by administration of a narcotic antagonist, e.g., naloxone. Evidence for critical involvement of excitatory aminoacid (glutamate), opioid receptors, and phosphorylation of proteins in these phenomena is summarized.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.681-682
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• 2023

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.77-77
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• 1993

약물 내성 (tolerance) 및 의존성 (dependence)은 그 약물이 지니고 있는 여러 가지 약리작용과 관련되어 형성된다. 약물의 반복투여 후, 나타나는 작용이 처음의 반응 (response) 보다 감소되어 나타나는 현상 즉, 내성과, 이와는 반대로 약물반복 투여 후 나타나는 작용이 처음의 반응보다 점점 증가하는 역내성 (reverse tolerance 또는 sensitization) 측정에 있어서 약물에 따라 적절한 검색 방법을 설명한다. 의존성에 있어서 약물 섭취 결과 mood가 변하거나 도취감 또는 만족감을 일으키게 되면 그 감각을 재 경험하고 싶다는 욕구가 일어나게 되는 정신적 의존성(psychic dependence)과, 약물을 반복 투여하다가 갑자기 투여를 중단 했을때 여러가지 생리학적인 또는 행동적인 변화가 급격히 증가하여 금단증상을 나타내는 신체적 의존성 (physical dependence) 측정 방법을 제시한다. 내성과 의존성은 근본적으로 다르지만 대부분의 경우 내성이 형성되면 의존성이 형성된다. 여기서는 주로 morphine과 psychostimulants를 투여한 후 나타나는 약리작용에 대한 내성과 opioids (마약성 진통제)의 의존성 평가 방법에 대한 model을 설명하고자 한다 진통성 내성(analgesic tolerance)에 있어서 진통제의 진통력은 진통력 측정 방법(tail pinch, paw-withdrawal, tail flick, tail-withdrawal, hot plate, writhing, etc)에 따라 차이가 있기 때문에 각각의 진통제의 정합한 내성 측정 방법을 결정할 필요가 있다. 역내성 (roversetolerance)은 cocaine, amphetamine, opioids둥의 만성투여에서 일어난다. 이들 역내성을 측정하는 한 방법으로 자발운동을 측정하는데 locomotor activity cage나 tilting cage를 이용한다. 정신적 의존성(psychic dependence)은 약물 섭취 욕구를 이용한 CPP (conditioned place preference)법을 소개한다. 신체적 의존성 (physical dependence)은 opioids를 만성적으로 투여한 후 naloxone으로 precipitation하여 나타난 여러 가지 금단증상을 측정하고 몇몇 평가 model을 제시한다.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.357-362
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• 2019

Limonene is a cyclic terpene found in citrus essential oils and inhibits methamphetamine- induced locomotor activity. Drug dependence is a severe neuropsychiatric condition that depends in part on changes in neurotransmission and neuroadaptation, induced by exposure to recreational drugs such as morphine and methamphetamine. In this study, we investigated the effects of limonene on the psychological dependence induced by drug abuse. The development of sensitization, dopamine receptor supersensitivity, and conditioned place preferences in rats was measured following administration of limonene (10 or 20 mg/kg) and methamphetamine (1 mg/kg) for 4 days. Limonene inhibits methamphetamine- induced sensitization to locomotor activity. Expression of dopamine receptor supersensitivity induced by apomorphine, a dopamine receptor agonist, was significantly reduced in limonenepretreated rats. However, there was no significant difference in methamphetamine-induced conditioned place preferences between the limonene and control groups. These results suggest that limonene may ameliorate drug addiction-related behaviors by regulating postsynaptic dopamine receptor supersensitivity.

• Korean Journal of Acupuncture
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• v.29 no.2
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• pp.179-187
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• 2012

Objectives : Since acupuncture was accepted as an useful therapy for the drug addiction, a lot of studies about acupuncture have been carried out. This study was performed to review the articles about morphine addiction which used acupuncture as a treatment and to interpret the use of acupoints from the viewpoint of Six-meridian (Yuk Gyeong, three yin and three yang) theory. Methods : The authors searched 255 articles in PubMed with the key word of "morphine, acupuncture" and 629 articles in KISS (Koreanstudies Information Service System) with the key word of "morphine". The articles written in English only were included. The articles related with morphine (abuse, dependence, sensitization, addiction, intake, withdrawal sign, withdrawal syndrome, reinstatement, craving) only were included. The articles which used manual- or electro-acupuncture only were included and auricular acupuncture was excluded. Both of clinical and experimental study were reivewed. Results : The most frequently used acupoint was ST36-SP6 (electroacupuncture), and the second was HT7. LI4 was the third, and BL23 and PC6 were also used. Conclusions : The acupoints used in the morphine study seem to influence the brain through diverse mechanisms and it is thought that control of the reaction against stress appears to be related with these mechanisms.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.111.1-111.1
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• 2002

• Archives of Pharmacal Research
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• v.18 no.2
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• pp.113-117
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• 1995

We re-cloned mouse ${\delt}-Opioid$receptor from NG108-15 cells using RT-PCR, and confirmed it by restriction analysis and by sequencing the beginning and end part of the amplified DNA. When transiently expressed in COS-7 cells, cloned ${\delt}-Opioid$ receptor showed saturable and specific binding to $[^3H]$naloxone with very similar binding parameters to originally reported ones. To make antibodies specific for the ${\delt}-Opioid$ receptor, the carboxy tail of the receptor, which is unique to the ${\delt}-Opioid$ receptor compared with other opioid receptors, was expressed in bacteria as a ufsion proteinwith glutathione S-transferase. Purified fusion protein selective for ${\delt}-Opioid$ receptor when tested by western blotting using membrane proteins prepared from transfected COS-7 cells. Cloned ${\delt}-Opioid$ receptor andl antibodies specific for ${\delt}-Opioid$ receptor are going to be valuable tools for studying pharmacological actions of the ${\delt}-Opioid$ receptor and morphine dependence.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.34-45
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• 1998

We provide the reader with a brief introduction to the neurobiology of neuropeptides. Several comprehensive reviews of the distribution and neurochemical, neurophysiological, neuropharmacological and behavioral effects of the major neuropeptides have recently appeared. In reviews of the large number of neuropeptides in brain and their occurance in brain regions thought to be involved in the pathogenesis of major psychiatric disorders, investigators have sought to determine whether alternations in neuropeptide systems are associated with schizophrenia, mood disorders, anxiety disorders, alcoholism and neurodegenerative disease. There is no longer any doubt that neuropeptide-containing neurons are altered in several neuropsychiatric disorders. One of the factors that has hindered neuropeptide research to a considerable extent is the lack of pharmacological agents that specifically alter the synaptic availability of neuropeptides. With the exception of naloxone and naltrexone, the opiate-receptor antagonists, there are few available neuropeptide- receptor antagonists. Two independent classes of neuropeptide-receptor antagonists has been expected to be clinically useful. Naltrexone, a potent ${\mu}$-receptor antagonist, has been used successfully to reduce the need for alcohol consumption. And cholecycstokinin antagonists are now in development as a new class of anxiolytics, which would be expected to be free from tolerance and physical dependence and lack of sedation. In this review, we deal with these two kinds of neuropeptide system, the opioid system and cholesystokinins in the brain. The role of opioid systems in the reinforcement after alcohol consumtion and that of cholesystokinins in the pathogenesis of anxiety will be discussed briefly. As we know, the future for neuropeptides in psychiatry remains bright indeed.