• 대한핵의학회지
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• 제35권4호
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• pp.258-267
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• 2001

Purpose/Methods: Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum uslng $[^3H]$]WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Results: Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 mg/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4 mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. Conclusion: These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli.

• Biomolecules & Therapeutics
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• 제12권1호
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• pp.9-18
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• 2004

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of ${\beta}$-carbolines (harmaline and harmalol) and deprenyl on the dopamine-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. Cell death due to 250 4{\mu}$M dopamine was inhibited by caspase inhibitors (z-IETD.fmk, z-LEHD.fmk and z-DQMD.fmk) and antioxidants (N-acetylcysteine, ascorbate, superoxide dismutase, catalase and carboxy-PTIO). ${\beta}$-Carbolines prevented the dopamine-induced cell death in PCl2 cells, while deprenyl did not inhibit cell death. ${\beta}$-Carbolines decreased the condensation and fragmentation of nuclei caused by dopamine in PC12 cells. ${\beta}$-Carbolines inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, formation of reactive oxygen species and depletion of GSH caused by dopamine in PC12 cells, whereas deprenyl did not decrease dopamine-induced mitochondrial damage. ${\beta}$-Carbolines, deprenyl and antioxidants depressed the formation of nitric oxide and melanin in dopamine-treated PC12 cells. The results suggest that cell death due to dopamine PC12 cells is mediated by caspase-8, -9 and -3. Unlike deprenyl, ${\beta}$-carbolines may attenuate the dopamineinduced cell death in PC12 cells by suppressing change in the mitochondrial membrane permeability through inhibition of the toxic action of reactive oxygen and nitrogen species.

• Archives of Pharmacal Research
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• 제18권4호
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• pp.249-255
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• 1995

The changes in the levels of the extracellular dopamine metabolites and the responses to various dopamine agents were studied by using microdialysis inhyperglycemic rat striatum. The hyperglycemia were induced by the administriation of streptozotocin (40 mg/kg, i.p. for 3 days.). The basal levels of striatal dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were significantly decreased in hyperglycemic rat striatum. After the administration ofl D-1 and D-2 receptor antagonists, SCH-23390 and (-)sulpiride, to rats 14 days after the last administration of STZ, the increased rates in DOPAC levels were higher in hyper- than in normoglycemic rats. However, after the administration of dopamine autoeceptor agonist, 3(-)PPP, the levels of the extracellular HVA were increased in normoglycemic rats, but those were not altered in hyperglycemic rats. The results indicate that the striatal dopamine activities were decreased in the hyperglycemic rats and suggest that release of dopamine may be decreased in hyperglycemic rats. Furthermore it suggest that the increase in the levels of the extracellular dopamine metabolites by dopamine antagonists might be dur to the incrrased sensitivities of the dopamine receptors in hyperglycemic state.

• 동의신경정신과학회지
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• 제14권1호
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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.

• Fisheries and Aquatic Sciences
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• 제14권4호
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• pp.379-388
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• 2011

The mechanism by which gonadotropin-releasing hormone (GnRH) and dopamine (DA) control gonadotropin (GTH) release was studied in male and female rainbow trout using cultured pituitary cells obtained at different reproductive stages. The mechanisms of follicle-stimulating hormone (FSH) release by GnRH and DA could not be determined yet. However, basal and salmon-type GnRH (sGnRH)- or chicken-II-type GnRH (cGnRH-II)- induced luteinizing hormone (LH) release increased with gonadal maturation in both sexes. LH release activity was higher after sGnRH stimulation than cGnRH-II stimulation at maturing stages in both sexes. The GnRH antagonist ([Ac-3, 4-dehydro-$Pro^1$, D-p-F-$Phe^2$, D-$Trp^{3,6}$] GnRH) suppressed LH release by sGnRH stimulation in a dose-dependent manner, although the effect was weak in maturing fish. The role of DA as a GTH-release inhibitory factor differs during the reproductive cycle: the inhibition of sGnRH-stimulated LH release by DA was stronger in immature fish than in maturing, ovulating, or spermiated fish. DA did not completely inhibit sGnRH-stimulated LH release, and DA alone did not alter basal LH release. Relatively high doses ($10^{-6}$ or $10^{-5}M$) of domperidone (DOM, a DA D2 antagonist) increased LH release, which did not change with reproductive stage in either sex. The potency of DOM to enhance sGnRH-stimulated LH release was higher in maturing and ovulated fish than in immature fish. These data suggest that LH release from the pituitary gland is controlled by dual neuroendocrine mechanisms by GnRH and DA in rainbow trout, as has been reported in other teleosts. The mechanism of control of FSH release, however, remains unknown.

• 동의생리병리학회지
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• 제17권2호
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• pp.510-517
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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 (5 mg/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.

• 생물정신의학
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• 제8권1호
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• pp.79-84
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• 2001

Objectives : To investigate the effects of (-)-3-PPP(0.5, 2, and 10mg/kg, s.c.) and haloperidol(0.1, 0.5, and 2mg/kg, s.c.) on the extracellular dopamine concentrations, and the effect of pretreatment with (-)-3-PPP(2mg/kg) on the haloperidol(2mg/kg)-induced extracellular dopamine concentrations in the nucleus accumbens(NAS) of free moving rats. Methods : Dopamine levels in dialysate were determined with high pressure liquid chromatography(HPLC) with electrochemical detection(ECD). Results : (1)(-)-3-PPP had dual actions depending on the doses: at 2mg/kg, it decreased and at 10mg/kg, increased extracellular dopamine concentrations ; (2) haloperidol at all doses increased dopamine levels with higher dose having a greater increase; and (3) pretreatment of (-)-3-PPP reduced the increase in dopamine levels elicited by acute treatment with haloperidol. Conclusions : These findings suggest that pretreatment of (-)-3-PPP in low dose could accelerate the onset of therapeutic effect of haloperidol by diminishing the haloperidol-induced dopamine release in the limbic system.

• 대한한의학방제학회지
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• 제22권1호
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• pp.105-112
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• 2014

Background and objective: Methamphetamine (Meth) is a widely abused psychostimulant that produces hyperlocomotion in rodents. Radix of Glycyrrhizae uralensis comprises a variety of bioactive components that have neuroprotective effects. In a previous study, we have demonstrated methanol extracts from radix of Glycyrrhizae uralensis (MEGR) suppress acute cocaine-induced extracellular dopamine release in the nucleus accumbens. In the present study, we investigated the effect of MEGR on acute Meth-induced hyperlocomotion. Methods: Male Sprague-Dawley rats were orally administered with MEGR (60 mg/kg and 180 mg/kg) 60 min prior to an intraperitoneal injection of Meth (1.0 mg/kg). Results: Behavioral analysis showed acute Meth greatly increased locomotor activities, while pretreatment with MEGR dose dependently inhibited the hyperlocomotion. In parallel, there were markedly increased levels of dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid in the nucleus accumbens tissues in Meth-treated rats, which were also almost completely reversed by 180 mg/kg MEGR. Conclusions: These results showed that radix of Glycyrrhizae uralensis attenuates Meth-induced hyperlocomotion by inhibiting dopamine synthesis and utilization, suggesting that radix of Glycyrrhizae uralensis might be effective in blocking the rewarding effect of Meth.

• 대한약리학회지
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• 제19권1호
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• pp.85-92
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• 1983

Intestine is innervated by an interconnected plexus of both sympathetic and parasympathetic nerve fibers. Sympathetic influence causes inhibition of intestinal motility mediated by both ${\alpha}-\;and\;{\beta}-adrenergic$ receptors. The mechanism of intestinal relaxation by ${\beta}-receptors$ has been extensively studied, but the function of ${\alpha}-receptors$ in intestinal motility is still unclear. Although it is suggested that catecholamine reduces acetylcholine release and this may play an important role in ${\alpha}-receptor$ mediated intestinal relaxation, there is no definite evidences about the mechanism and site of action of ${\alpha}-receptor$ mediated relaxation. In this experiment, therefore, the effect and site of action of ${\alpha}-receptor$ agonists were investigated in the guinea pig ileum using electrical field stimulation. The results are summarized as follows : 1) Electrical field stimulation elicited tonic contraction in isolated guinea pig ileum ana this contraction was completely inhibited by the pretreatment of tetrodotoxin or atropine. 2) Norepinephrine, epinephrine and dopamine inhibited the contraction induced by electrical field stimulation but methoxamine and phenylephrine had little effects. 3) Inhibitory effects of norepinephrine and dopamine was partially blocked by yohimbine and phentolamine pretreatment. But haloperidol and propranolol pretreatment cause no effects on the electrical field stimulation induced contraction. Inhibitory effect of dopamine was completely blocked by both haloperidol and yohimbine pretreatment. 4) Inhibitory effects of norepinephrine and dopamine were little affected by the pretreatment with hexamethonium. It is suggested that electrical field stimulation causes tonic contraction of guinea pig ileum by releasing acetylcholine from postganglionic fiber, and this release is blocked by presynaptic ${\alpha}-receptor$ activation.

• 동의생리병리학회지
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• 제19권4호
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• pp.982-992
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• 2005

Acupuncture as a therapeutic intervention is widely used for the treatment of many functional disorders such as substance abuse and mental dysfunction. Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug addiction. Yet, there are still many unanswered questions about the basic mechanism of acupuncture. Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and raised the possibility that both of these effects may De linked to the same or closely overlapping the mesolimbic dopamine systems. Neiguan (PC6) point on the pericardium channel which is associated with the brain and its mental function, has been used to treat mental, psychosomatic disorders and gastroenterological disorders. The present study was designed to investigate the effect of acupuncture on repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and to measure the effect of acupuncture on repeated morphine-induced behavioral changes. 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 (5 mg/kg, s.c.). Acupuncture was applied at bilateral Neiguan (PC6) points for 1min after the morphine challenge. Results showed that acupuncture at the specific acupoint PC6, but not at control points (tail and HE8) significantly decreased both dopamine release, behavior induced by a systemic morphine challenge or a single s.c. morphine injection in the morphine-repeated animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts. Moreover, in a more general sense these results suggest that acupuncture can be used as a therapeutic intervention for correcting reversible malfunction of the body by direction of brain pathway and thus acupuncture can contribute to the biochemical balance in the central nervous system by regulating neurotransmitters.