• The Journal of Korean Medicine
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• v.29 no.4
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• pp.55-67
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• 2008

Objectives: The purpose of this study was to investigate the effect of Hwangryunhaedok-tang, its major component Coptidis Rhizoma, and the major component of Coptidis Rhizoma, berberine, on the expression of behavioral sensitization induced by the repeated administration of nicotine. Methods: Experimental ratswere divided into 3 groups and each group treated with saline, nicotine, and Hwangryunhaedok-tang. Experiments were performed on 4 further groups, each group treated with saline, nicotine, Coptidis Rhizoma, and berberine. To obtain rats addicted todrugs, nicotine was injected repeatedly. After 3 days of withdrawal phase, on the 11th day, rats were re-exposed to nicotine and thus able to induce the expression of the activity sensitization phenomenon successfully. To examine the change of c-Fos in the brain of experimental rats with the nicotine-induced activity sensitization, their neurological activation rate was assessed by c-Fos staining with Fos-like immunihistochemistry of the dopamine releasing area, the striatum and the nucleus accumbens. Results: The result demonstrate that Hwangryunhaedok-tang, its major component Coptidis Rhizoma and berberine,the major component of Coptidis Rhizoma, significantly reduced the walking activity rate in the drug addict models induced by nicotine administration, and Coptidis Rhizoma and its major component berberine reduce the marker of the neurological activation c-Fos, and thus revealed an effect of suppressing drug addiction. Conclusions: These results suggest the possibility of Hwangryunhaedok-tang, its major component Coptidis Rhizoma and the major component of Coptidis Rhizoma, berberine,as therapeutic for nicotine addiction.

• Anxiety and mood
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• v.10 no.2
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• pp.85-94
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• 2014

Non-pharmacological treatments have long been used for paraphilia or sexual offenders, but few clinical studies were conducted. However, recently there were issued cognitive behavioral therapy of paraphilia or sexual offenders based on the research findings obtained so far. In addition, there were the changes of Diagnostic and Statistical Manual of Mental Disorder by American Psychiatric Association at 2014. The methods of cognitive behavioral therapy for paraphilia or sexual offenders were electric aversion therapy, olfactory aversion therapy, ammonia aversion therapy, covert sensitization, masturbatory reconditioning, directed masturbation, verbal satiation, social skill training, assertiveness training etc. By synthesizing the newly reported foreign guidelines for treatment and review articles, the aim of this study is to investigate the non-pharmacologic therapies used for treatment of paraphilia or sexual offenders.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.84.1-84.1
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• 2003

Methamphetamine is a powerful stimulant that appears to produce locomotor activity and behavioral sensitization. Previous study has indicated that dopaminergic receptors are implicated in the behavioral responses of methamphetamine. Recently, it has been reported that other receptors, especially, M1 muscarinic acetylcholine receptor (M1R) plays an important role in the regulation of behavioral responses, and this receptor is abundantly expressed in brain regions, including the cerebral cortex, striatum, and the hippocampus of the animal. (omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.756-763
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• 2002

We have previously demonstrated that repeated injections of nicotine produced an increase in locomotor activity, dopamine(DA), release and c-Fos expression in the nucleus accumbens, one of the major projection areas of the central DA system. Acupuncture as a therapeutic intervention is widely used for the treatment of many functional disorders such as substance abuse and mental dysfunction. And many studies have shown that Coptidis Rhizoma has a suppressive effect on the central nervous system (CNS) and can affect the neurotransmitter systems in the CNS. In order to investigate whether acupuncture and Coptidis Rhizoma have an influence on nicotine-induced reinforcing and behavioral effects, we examined the effect of zusanli(ST36) and Coptidis Rhizoma on repeated nicotine-induced locomotor activity, and zusanli(ST36) on c-Fos expression as an important maker of postsynaptic neuronal activity in nucleus accumbens. Male SD rats received Coptidis Rhizoma (100mg/kg, p.o.) 30 min before injections of nicotine (0.4 mg/kg, s.c.) for 7 days. Rats were followed withdrawal for 3 days and one challenge for 1 day. Systemic challenge with nicotine produced a much larger increase in locomotor activity. Pretreatment with acupuncture at zusanli(ST36, 100Hz) and Coptidis Rhizoma decreased in nicotine-induced locomotor activity. These results demonstrated that reduction in locomotor activity by acupuncture at zusanli(ST36, 100Hz) and Coptidis Rhizoma may be mediated by reduction of dopamine release. Our results suggest that acupuncture at zusanli(ST36, 100Hz) and Coptidis Rhizoma may have therapeutic effect on nicotine addiction.

• Archives of Pharmacal Research
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• v.28 no.9
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• pp.995-1001
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• 2005

Morphine-induced analgesia has been shown to be antagonized by ginseng total saponins (GTS), which also inhibit the development of analgesic tolerance to and physical dependence on morphine. GTS is involved in both of these processes by inhibiting morphine-6-dehydrogenase, which catalyzes the synthesis of morphinone from morphine, and by increasing the level of hepatic glutathione, which participates in the toxicity response. Thus, the dual actions of ginseng are associated with the detoxification of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contractions in guinea pig ileum (I-L-receptors) and mouse vas deferens $(\delta-receptors)$ are not mediated through opioid receptors, suggesting the involvement of non-opioid mechanisms. GTS also attenuates hyperactivity, reverse tolerance (behavioral sensitization), and conditioned place preference induced by psychotropic agents, such as methamphetamine, cocaine, and morphine. These effects of GTS may be attributed to complex pharmacological actions between dopamine receptors and a serotonergic/adenosine $A_{2A}1\delta-opioid$ receptor complex. Ginsenosides also attenuate the morphine-induced cAMP signaling pathway. Together, the results suggest that GTS may be useful in the prevention and therapy of the behavioral side effects induced by psychotropic agents.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.130.2-130.2
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• 2003

The present study was undertaken to examine the hypothesis that $\mu$-opioid receptors play a crucial role in behavioral sensitization to nicotine using $\mu$-opioid receptor knockout mice. All mice were treated acutely or repeatedly with nicotine 0.05 mg/kg twice daily for 7 consecutive days. The mice were challenged with nicotine on day 11. And locomotor activity was measured for 30min. (omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.767-773
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• 2004

Substantial evidence suggests that repeated injections of nicotine produce increase in locomotor activity and expression of the immediate-early gene, c-fos in the dopaminergic target areas. Herbal medicine as a therapeutic intervention has been widely used for the treatment of mental dysfunction. Many studies have shown that Cortex Phellodendris (CP) can affect the biochemical balance in the central nervous system. In order to investigate whether CP have an influence on their nicotine-induced behavioral sensitization, we examined the effect of CP on nicotine-induced locomotor activity and c-Fos expression in the striatum and nucleus accumbens utilizing the Fos-like immunohistochemistry (FLI). Male SD rats received CP (200㎎/㎏, i.p.) 30 min before repeated daily injections of nicotine (0.4㎎/㎏, s.c.) for 7 days. Rats were followed withdrawal for 3 days and one challenge for 1 day. System challenge with nicotine produced a much larger increase in locomotor activity and accumbal FLI. Pretreatment with CP significanly inhibited nicotine-induced locomotor activity and FLI in the striuatum and nucleus accumbens. These results demonstrated that reduction in locomotor activity by CP may be reflected by reduction of dopamine release and postsynaptic neuronal activity in the striatum and nucleus accumbens. Our results suggest that CP may have therapeutic effect on nicotine addiction. Supported by a fund (99-PJ9-PG1-002-0004).

• Proceedings of the PSK Conference
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• 2003.10a
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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)

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.45-51
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• 2011

These experiments were designed to use typical makers from behaviors and molecular basis in addicted animals of morphine and cocaine. Morphine has been widely abused with a high physical dependence liability. Morphine withdrawal activates the intracellular cAMP signaling pathway and further leads to changes in the expression of the cAMP response element binding protein (CREB), which may be important to the development and expression of morphine dependence. From these experiments, repeated morphine (10 mg/kg, twice per day for 7 days) developed physical dependence. Withdrawal signs were precipitated by naloxone and also increased the expression of the CREB. In addition, repeated exposure of cocaine (15 mg/kg) to mice develops locomotor sensitization and produced lasting behavioral sensitivity. Cocaine- and amphetamine-regulated transcript peptide (CART) peptide was up-regulated by repeated administration of cocaine in the striatum. Therefore, repeated morphine induced the development of physical dependence and increased pCREB. In addition, repeated cocaine induced locomotor sensitization and over-expressed CART peptide. In conclusion, the development of physical dependence and pCREB for morphine, and locomotor sensitization and CART peptide over-expression for cocaine would be useful markers to predict the abuse potential of opioid analgesics and pychostimulant drugs in animals, respectively.

• Journal of Oriental Neuropsychiatry
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• v.14 no.1
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• pp.85-106
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• 2003

Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and it is suggested that both of these effects are mediated by the same or closely overlapping dopamine systems. Specifically, the mesolimbic dopamine system has been implicated in the reinforcing and sensitizing properties of morphine. In oriental medicine, Shenmen (HT7) point on the heart channel has been used to treat mental and psychosomatic disorders. This study was designed to investigate the effect of acupuncture on acute and repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and morphine-induced behavioral changes. In the morphine sensitization experiment, male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5mg/kg, s.c.). Acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after the morphine challenge. In the acute experiment, rats also received acupuncture for 1 min after an injection of morphine hydrochloride (5 mg/kg, s.c.). Results showed that acupuncture at the specific acupoint HT7, but not at control points (tail) significantly decreased both dopamine release and behavior induced by a systemic morphine challenge or a single sc morphine injection in the acute animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts.