• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.95-101
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• 1997

The recent hypothesis about the pathophysiology of schizophrenia has been centered mainly on two theories, i.e. dopamine hypothesis and serotonin hypothesis. We investigate the correlations between plasma monoamine metabolite concentrations and clinical symptoms in schizophrenic patients. The first purpose of our study was to examine whether the plasma levels of HVA(homovanillic acid) and 5-HIAA(hydroxyindoleacetic acid) are significantly different in schizophrenics, compared to normal controls. And, with the intention of clarifying the interaction between dopaminergic system and serotoninergic system, the ratio of HVA/5-HIAA also was measured. The second purpose was whether the basal(pre-treatment) levels of these metabolites show the correlation with clinical symptoms. Finally, third purpose was whether basal HVA and 5-HIAA levels can be held as a predictor of treatment response. We used Scale for the Assessment of Positive Symptoms(SAPS) and Scale for the Assessment of Negative Symptoms(SANS) as the clinical symptom rating scales. Our results were as followed, 1) only the level of basal plasma HVA was significantly differ in schizophrenics. 5-HIAA and HVA/5-HIAA were not. 2) basal HVA showed significant correlation with SAPS score, especially delusion subscale. 3) the higher was the basal HVA level, the more improvement in clinical symptoms was observed. The basal 5-HIAA level and the HVA/5-HIAA ratio did not show any significant findings. These results support the dopamine hypothesis of schizophrenia, but fail to examine on the possible involvement of serotonin in schizophrenia.

• Science of Emotion and Sensibility
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• v.16 no.3
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• pp.319-332
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• 2013

Previous research on learning and memory has focused on how they are constructed through past experiences. Recent studies, however, have shed light on that such cognitive processes are in service of higher goals of maximizing future rewards. This review paper aims to introduce and discuss a related line of research. First, this paper introduces researches that show goal-directed model-based reinforcement learning, in which agents choose a behavior that does not necessarily bring immediate rewards but will allow future rewards, based on generalization and analogical extrapolation. It also reviews studies on neural substrates of goal-directed learning, and discusses that cognitive process implicated in striatal dopaminergic signals can also influence memory. Especially, memory is not a merely passive process of storing and retrieving past experiences homogeneously, but rather results of a decision-making process to serve higher goals. The body of research suggests that information on future rewards can have influence on current cognitive processing in a retrospective manner.

• The Journal of Internal Korean Medicine
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• v.35 no.3
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• pp.298-308
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• 2014

Objectives: In this study we made an effort to investigate the protective effect of SSMT on the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced cytotoxicity of SH-SY5Y cells. Methods: The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MMT) assay. The fluorescence intensity was measured by using a dye and then with propidium iodide (PI) DNA flow cytometry analysis of the effects on the cell cycle of the SH-SY5Y cells and were used to measure the fluorescence of intracellular reactive oxygen species generation by MPTP. Results: Pretreatment of SSMT significantly suppressed MPTP-induced cytotoxicity, which was revealed as apoptosis characterized by the reduction of cell viability, the increase of ROS production, and the loss of mitochondrial membrane potential in SH-SY5Y cells. Conclusions: These findings suggest that SSMT exerts neuroprotective effects on human neuroblastoma SH-SY5Y cells by MPTP-induced dopaminergic neurodegeneration.

• The Korean Journal of Pain
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• v.14 no.1
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• pp.46-50
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• 2001

Background: Ondansetron is both a central and peripheral serotonin (5HT) receptor antagonist and droperidol is a dopaminergic blocking drug which acts centrally at the chemoreceptor trigger zone. We assessed the efficacy and adverse effects of ondansetron, droperidol or both, in the prevention of postoperative emesis during postoperative intravenous patient-controlled analgesia (PCA) using butorphanol and ketorolac medication. Methods: We studied 60 women, aged 25-60 yrs, who underwent total abdominal hysterectomy (TAH), under general anesthesia using $N_2O-O_2$-enflurane. A bolus dose of 1 mg of butorphanol and 4 mg of ondansetron were given to patients and thereafter, PCA was started using 10 mg of butorphanol and 240 mg of ketorolac mixed into the 5% D/W solution (total volume; 100 ml, 1 ml of bolus dose, and 10 min of lockout interval). We also added ondansetron 4 mg (Group O, n = 20), ondansetron 4 mg and droperidol 2.5 mg (Group OD, n = 20), or droperidol 2.5 mg (Group D, n = 20) to the PCA drug. The severity of pain, nausea, vomiting, sedation and other side effects were assessed at 0, 1, 2, 6, 12, 24, 36 and 48 hr after awakening. Results: There was no difference in the incidence of nausea and vomiting between the three group [Group O: 4 (20%) and 3 (15%), respectively; Group OD: 1 (5%) and 1 (5%), respectively; Group D: 3 (15%) and 3 (15%), respectively]. Group O showed a lower sedation score than the other groups (P < 0.05). The pain score and other side effects did not show any difference between the groups. Conclusions: The combination of ondansetron and droperidol showed no clinical benefit compared with ondansetron or droperidol alone for prevention of postoperative nausea and vomiting during postoperative PCA using butorphanol and ketorolac.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.5
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• pp.263-268
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• 2005

Striatum has important roles in motor control, habitual learning and memory. It receives glutamatergic inputs from neocortex and thalamus, and dopaminergic inputs from substantia nigra. We examined effects of dopamine (DA) on the corticostriatal synaptic transmission using in vitro extracellular recording technique in rat brain corticostriatal slices. Synaptic responses were elicited by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. Corticostriatal population spike (PS) amplitudes were decreased ($39.4{\pm}7.9$%) by the application of $100{\mu}M$ DA. We applied receptor subtype specific agonists and antagonists and characterized the modulation of corticostriatal synaptic transmission by different DA receptor subtypes. $D_2$ receptor agonist (quinpirole), antagonist (sulpiride), and $D_1$ receptor antagonist (SKF 83566), but not $D_1$ receptor agonist (SKF 38393), induced significantly the reduction of striatal PS. Pretreatment neither with SKF 83566 nor sulpiride significantly affected corticostriatal synaptic inhibition by DA. However, the inhibition of DA was completely blocked by pretreatment with mixed solution of both SKF 83566 and sulpiride. These results suggest that DA inhibits corticostriatal synaptic transmission through both $D_1$ and $D_2$ receptors in concert with each other.

• Anxiety and mood
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• v.2 no.1
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• pp.45-49
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• 2006

Puropse : Disturbances of dopaminergic system might be related to the possible mechanism of panic disorder. This study was aimed to examine the association of DRD2 Taq 1 polymorphism and panic disorder. Methods : One hundred and fourteen patients with panic disorder (62 male (54.4%), mean age $40.96{\pm}0.11$ years) and 200 comparison subjects (114 male (57.0%), mean age $35.57{\pm}8.81$ years)were tested for DRD2 TaqI A polymorphism. We excluded panic patients with comorbid alcohol related disorders, bipolar disorders, and any kinds of psychotic disorders because there have been some reports about association of these disease and DRD2 TaqI A polymorphism. Results : There was significant difference in the frequency of the genotype in DRD2 polymorphism between patients and controls (${\chi}^2$=6.09, df=2, p=0.048). The A1+ allele (A1A1 and A1A2) frequency analysis also showed significant association (${\chi}^2$=4.08, df=1, p=0.043). In addition, we observed a more strong and specific association between panic disorder and the A1+ allele of the DRD2 TaqI polymorphism for men (${\chi}^2$=4.71, df=1, p=0.03), but not for women (${\chi}^2$=0.45, df=1, p=0.50). Conclusion : These results in our Korean sample suggest that the DRD2 TaqI A polymorphism may be associated with panic disorder. Furthermore, we found sex-specific association of DRD2 A1 allele with panic disorder.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.147-151
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• 2009

Repeated psychostimulants induce electroencephalographic (EEG) changes, which reflect adaptation of the neural substrate related to dopaminergic pathways. To study the role of dopamine receptors in EEG changes, we examined the effect of apomorphine, the dopamine D1 receptor antagonist, SCH-23390, and the D2 receptor antagonist, haloperidol, on EEG in rats. For single and repeated apomorphine treatment groups, the rats received saline or apomorphine for 4 days followed by a 3-day withdrawal period and then apomorphine (2.5 mg/kg, i.p.) challenge after pretreatment with saline, SCH-23390, or haloperidol on the day of the experiment. EEGs from the frontal and parietal cortices were recorded. On the frontal cortex, apomorphine decreased the power of all the frequency bands in the single treatment group, and increased the theta (4.5 ${\sim}$ 8 Hz) and alpha (8 ${\sim}$ 13 Hz) powers in the repeated treatment group. Changes in both groups were reversed to the control values by SCH-23390. On the parietal cortex, single apomorphine treatment decreased the power of some frequency bands, which were reversed by haloperidol but not by SCH-23390. Repeated apomorphine treatment did not produce significant changes in the power profile. These results show that adaptation of dopamine pathways by repeated apomorphine treatment could be identified with EEG changes such as increases in theta and alpha power of the frontal cortex, and this adaptation may occur through changes in the D1 receptor and/or the D2 receptor.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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• pp.1640-1647
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• 2015

We recently reported that the antimicrobial peptide Lumbricusin (NH₂-RNRRWCIDQQA), isolated from the earthworm, increases cell proliferation in neuroblastoma SH-SY5Y cells. Here, we investigated whether Lumbricusin has neurotropic activity in mouse neural stem cells (MNSCs) and a protective effect in a mouse model of Parkinson's disease (PD). In MNSCs isolated from mouse brains, Lumbricusin treatment significantly increased cell proliferation (up to 12%) and reduced the protein expression of p27^Kip1 through proteasomal protein degradation but not transcriptional regulation. Lumbricusin inhibited the 6-OHDA-induced apoptosis of MNSCs, and also showed neuroprotective effects in a mouse PD model, ameliorating the motor impairments seen in the pole, elevated body swing, and rotation tests. These results suggest that the Lumbricusin-induced promotion of neural cell proliferation via p27^Kip1 degradation has a protective effect in an experimental PD model. Thus, the antimicrobial peptide Lumbricusin could possibly be developed as a potential therapeutic agent for the treatment of PD.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.89-97
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• 2013

Developing an animal model for a specific disease is very important in the understanding of the underlying mechanism of the disease and allows testing of newly developed new drugs before human application. However, which of the plethora of experimental animal species to use in model development can be perplexing. Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a very well known method to induce the symptoms of Parkinson's disease in mice. But, there is very limited information about the different sensitivities to MPTP among mouse strains. Here, we tested three different mouse strains (C57BL/6, Balb-C, and ICR) as a Parkinsonian model by repeated MPTP injections. In addition to behavioral analysis, endogenous levels of dopamine and tetrahydrobiopterin in mice brain regions, such as striatum, substantia nigra, and hippocampus were directly quantified by liquid chromatography-tandem mass spectrometry. Repeated administrations of MPTP significantly affected the moving distances and rearing frequencies in all three mouse strains. The endogenous dopamine concentrations and expression levels of tyrosine hydroxylase were significantly decreased after the repeated injections, but tetrahydrobiopterin did not change in analyzed brain regions. However, susceptibilities of the mice to MPTP were differed based on the degree of behavioral change, dopamine concentration in brain regions, and expression levels of tyrosine hydroxylase, with C57BL/6 and Balb-C mice being more sensitive to the dopaminergic neuronal toxicity of MPTP than ICR mice.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.6
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• pp.281-286
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• 2002

To understand the cytotoxic mechanism of $MPP^+,$ we examined the involvement of ceramide in $MPP^+-induced$ cytotoxicity to human neuroblastoma SH-SY5Y cells. When SH-SY5Y cells were exposed to $MPP^+,\;MPP^+$ induced dose-dependent cytotoxicity accompanied by 2-fold elevation of intracellular ceramide levels in SH-SY5Y cells. Three methods were used to test the hypothesis that the elevated intracellular ceramide is related to $MPP^+-induced$ cytotoxicity: $C_2-ceramide$ was directly applied to cells, sphingomyelinase (SMase) was exogenously added, and oleoylethanolamine (OE) was used to inhibit degradation of ceramide. Furthermore, inhibition of ceramide-activated protein phosphatase (CAPP), the effector of ceramide, using okadaic acid (OA) attenuated cell death but treatment of fumonisin $B_1,$ the ceramide synthase inhibitor, did not alter the cytotoxic effect of $MPP^+.$ Based on these, we suggest that the elevation of intracellular ceramide is one of the important mediators in $MPP^+-induced$ cell death.