• Korean Journal of Biological Psychiatry
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• v.7 no.1
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• pp.55-63
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• 2000

Avariety of symptoms can occur following traumatic brain injury(TBI) or other types of acquired brain injury. These symptoms can include problems with short-term memory, attention, planning, problem solving, impulsivity, disinhibition, poor motivation, and other behavioral and cognitive deficit. These symptoms may respond to certain drugs, such as dopaminergic agents. Amantadine may protect patients from secondary neuronal damage after brain injury as a effect of NMDA receptor antagonists and may improve functioning of brain-injured patients as a dopaminergic agonist. Clinically, based on current evidence, amantadine may provide a potentially effective, safe, and inexpensive option for treating the cognitive, mood, and behavioral disorders of individuals with brain injury. The rationales for using amantadine are discussed, and pertinent literatures are reviewed.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.613-617
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• 2001

The present study examined the hypothesis that NMDA, AMPA/Kainate, and metabotropic (mGlu) glutamate receptors contribute to a behavioral stimulation induced by activation of dopamine receptors by comparing responses in apomorphine-induced cage climbing behaviors in mice. MK-801, CNQX, and MCPG were served as the NMDA receptor, AMPA/Kainate receptor, and mGlu receptor antagonist, respectively, to elucidate the glutamatergic modulation in apomorphine-induced eopaminergic activation in mice. Drugs were administered intracerebroventricularly (i.c.v.) into the mouse brain 15 min before the apomorphine treatment (2 mg/kg, s.c.). 1.c.v. injection of MK-801 inhibited the apomorphine-induced cage climbing behavior dose-dependently. However, treatments with CNQX and MCPG did not any significant change in apomorphine-induced cage climbing behavior in mice. These results suggest that stimulation of NMDA type of glutamate receptors could contribute to the dopaminergic sti mutation, but not AMPA/Kainate and mGlu type glutamate receptors.

• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.48-53
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• 1997

CV(bDAT) cell line, expressing dopamine transporter stably, has been established by transfection of CV-1 cells with bovine dopamine transporter cDNA. Using CV(bDAT) cells, the effects of various antipsychotic drugs on dopamine uptake activity were investigated. All of antipsychotic drugs tested, inhibited the [$^3H$]dopamine uptake into CV(bDAT) cells with $IC_{50}s$ in the low to mid micromolar range, implying that antipsychotic drugs may produce overflow of dopamine in the synaptic cleft of dopaminergic neuron.

• Korean Journal of Oriental Medicine
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• v.15 no.3
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• pp.53-61
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• 2009

Oxytocin(OT), classically known to stimulate labour and milk ejection, contributes to play an important role in a wide range of behavioral effects including drug addiction. An increasing body of evidence suggests that OT ameliorates acute and long-term effects of commonly used drugs by means of interacting with the mesolimbic dopamine system. Mesolimbic dopamine system is thought to play a major role in the reinforcing properties of drug abuse. Oxytocin receptors in the nucleus accumbens(NAc) and ventral tegmental area(VTA) have been implicated in the regulation of reinforcing effects in abused drugs. In the same way acupuncture may attenuate the reinforcing effects of abused drugs in the NAc and VTA. We have an interest in similar liaison between the substrates of acupuncture and drug addiction that may involve OT. Here, we described the possibility that acupuncture modulates the reinforcing and sensitizing properties of abused drugs in the dopaminergic system via the regulation of activities in the oxytocinergic system. The elements in this paper are summarized as follows : neuroanatomical studies of oxytocinergic innervation and distribution of oxytocin receptors; experiments related to the methamphetamine, cocaine, morphine and ethanol; experiments related to the oxytocin and acupuncture.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.101-107
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• 2004

Repeated administration of psychostimulants such as amphetamines increases locomotor activity in rodents. These drugs, including methamphetamine, enhance dopaminergic neurotransmission and result in hyper-locomotion and behavioral sensitization. It is well known that the existence of a complex balance between the cholinergic and dopaminergic systems in the central nervous system. Thus, behavioral sensitization by methamphetamine may be related to the expression of the M1 muscarinic acetylcholine receptors gene. The present study investigated the changes of M1R mRNA in hyperlocomotor activity and behavioral sensitization by methamphetamine (2 mg/kg) in mice. Our results showed that M1R mRNA expression was increased in the frontal cortex and the hippocampus region (the CA2 region) in the acute methamphetamine administered group compared to the saline administered group. In the chronic group, M1R mRNA expression was increased in the frontal cortex ill1d the hippocampus regions (CA2 and DG regions) in melt1amphetamine administered group compared to saline control group. These results indicate that acute or chronic treatment of mathamphetamine leads to the region-specific changes in mRNA expression levels of M1R. Therefore, Therefore, the present result suggests that M1R may play a role in modulating of methamphetamine-induced behavioral sensitization in mice.

• Animal cells and systems
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• v.16 no.1
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• pp.20-26
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• 2012

Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.

• Proceedings of the Ginseng society Conference
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• 2005.11a
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2005.11a
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• pp.49-66
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• 2005

Panax 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. GTS inhibited morphine-6 dehydrogenase, which catalyzes production of mophinone from morphine, and increased hepatic glutathione level responsible to toxicity. Therefore, we hypothesized 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.

• Archives of Pharmacal Research
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• v.9 no.3
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• pp.169-174
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• 1986

Bilateral lesion of nucleus accumbens septi (N, AB), one of the mesolimbic nuclei, resulted in hyperirritability and muricide including mouse eating behavior in rats. The effects of various drugs on hyperirritability and muricide induced by NAB lesion were investigated in rats. Hyperirritability in NAB rats were significantly reduced by L-DOPA L-5-HTP major and minor tranquilizers but not reduced by MA, ATP and imipriamine-like antidepressants. On the other hand, muricide in NAB rats was significantly suppressed by L-DOPA, L-5-HTP, major and minor tranquilizers, furthermore, selectively suppressed by MA, ATP and antidepressants. These results suggested that the neural mechanism for inducing muricide is distinct from for hyperirritability in NAB rats, and that muricide in NAB rats is resulted from the increasing of cholinergic activity and reduction of dopaminergic and serotonergic activity.

• YAKHAK HOEJI
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• v.59 no.3
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• pp.127-134
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• 2015

The aim of this study was to investigate the correlation among age, symptoms and initial medication (IM), and the tolerance duration of IM in Korean people with Parkinson's disease (PD). We studied 60 patients with untreated early PD who were initially diagnosed in our hospital between Jun 2006 and Sep 2014. We collected data on sex, age at diagnosis, symptom duration until diagnosis, main motor symptoms, frequency and duration of IM through electronic medical records. We divided patients into groups depending on the number of drugs (MONO/COMBI) and whether to contain dopaminergic property (DOPA/NDOPA). We analyzed the correlation between age and symptoms in each two groups and calculated the mean tolerance duration of IM in each of the groups. The mean symptom duration until diagnosis was 12.2 months. The most frequent drug was levodopa formulations (80%) compared to dopamine agonists (58.3%). The number of patients in the COMBI group (63.3%) was more than that in the MONO group (36.7%). Half of the patients in the COMBI group were taking LDF+DA (50%). Except for tremor, no other symptom showed a significant correlation between with IM. The mean tolerance duration of IM was within 200 days. The mean duration for COMBI group (342.7 days) was longer than that for MONO group (209.8 days). Among regimens, the mean tolerance duration of DOPA group (293.3 days) was longer than for NDOPA group (251.4 days). There was no difference in survival curves between any of the two groups. We found that patients experienced symptoms for over a year in Korea. This indicates that diagnosis time is faster than reported in other previous studies. The longest tolerance duration among IM was for dopaminergic combination therapy. More research is needed to design the most appropriate treatment for PD in Korean patients.