• Korean Journal of Biological Psychiatry
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• v.7 no.2
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• pp.159-163
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• 2000

Background : Dopamine receptors are strong candidates for involvement in schizophrenia and are target of a wide variety of antipsychotics. Dopamine $D_5$ receptor(DRD5) gene polymorphisms may be associated with various treatment response. The purpose of our study was define to what significance can be held as a predictor of treatment response in this polymorphism. Method : The total number of 116 Korean chronic schizophrenic patients was assessed after 48 weeks treatment. The Positive and Negative Syndrome Scale(PANSS) was rated for the clinical response to various antipsychotics. With the use of polymerase chain reaction amplification, we assessed this dopamine $D_5$ receptor polymorphism in schizophrenic patients who had been treated with antipsychotics, and related genotype with treatment response, to test the hypothesis that DRD5 polymorphism may lead to varying response to antipsychotics. Result : DRD5 polymorphism was not associated with treatment response to a variety of antipsychotics in chronic schizophrenic patients. Conclusion : Genetic variation of $D_5$ receptors do not predict treatment response to antispychotics.

• Korean Journal of Biological Psychiatry
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• v.12 no.2
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• pp.107-113
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• 2005

Purpose:In an attempt to predict the interpersonal differences of therapeutic response to antipsychotic drugs on pharmaco-genetic bases, this study was designed to investigate the relationship between the therapeutic response to antipsychotic drugs and Taq I A dopamine $D_2$ receptor polymorphism in schizophrenic patients. Methods:The subjects were 158 patients diagnosed with schizophrenia(DSM-IV). The therapeutic response to antipsychotic drugs was evaluated using the Treatment Response Scale(TRS) retrospectively. Patients were divided into two groups, dopamine receptor antagonist responders, and serotonin-dopamine antagonist responders. The patients' Taq I A dopamine $D_2$ receptor polymorphism was determined by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP). Results:The dopamine receptor antagonist responders had the A1 allele in significantly higher incidences (${\chi}^2$(1)=4.875, p=0.027, two-tailed). No significant difference was found among the serotonin-dopamine antagonist responders between those with or without the A1 allele. Conclusions:The patients with the A1 allele responded better to dopamine receptor antagonists than those with no A1 allele. Based on these results, it is suggested that the pharmacological effect of dopamine receptor antagonists can be predicted depending on the presence of the A1 allele in schizophrenic patients.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.218-224
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• 1997

The results regarding an association between the polymorphism sites in the dopamine $D_1$ receptor gene and schizophrenia compelled us to study the distribution of the polymorphism in Korean schizophrenia and controls. Eighty-eight schizophrenic patients and normal controls were examined by case-control study for distribution of the polymorphism of the dopamine $D_1$ receptor gene in Korean popualtion to minimize the effect of racial differencies in gene frequencies. The frequencies of the $B_1$ and $B_2$ in schizophrenic patients were 0.11 and 9.89, respectively. And 0.10 and 0.90 in normal control. Ther was no significant differences in the frequencies in the allele $B_1$ and $B_2$between schizophrenic patients and normal controls. The author present here the evidence of a lack of alleic association between the polymorphism of the dopamine $D_1$ receptor gene and Korean schizophrenic patients. The assumption that the dopamine $D_1$ receptor gene has a genetic role in the development of schizophrenia was not suppoorted by this case-control study.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.421-426
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• 1997

We evaluated the in vivo kinetics, distribution, and pharmacology of N-(4-[$^{18}F$]fluoromethylbenzyl)spiperone ([$^{18}F$]FMBS), a newly developed derivative of spiperone, as a potentially more selective radiotracer for the dopamine (DA) $D_2$ receptors. Mice received 1.9-3.7 MBq (1.8-3.6 nmol/kg) of [$^{18}F$]FMBS by tail vein injection. The time course and regional distribution of the tracer in brain were assessed. Blocking studies were carried out by intravenously preinjecting DA $D_2$ receptor blockers (spiperone, butaclamol) as well as drugs with high affinity for DA $D_1$ (SCH 23390), DA transporter (GBR 12909), and serotonin $S_2$ ($5-HT_2$) (ketanserin) sites. After injection of the tracer, the radioactivity in striatum increased steadily over time, resulting in a striatal-to-cerebellar ratio of 4.8 at 120 min postinjection. By contrast, the radioactivity in cerebellum, frontal cortex, and remaining cortex washed out rapidly. Preinjection of unlabeled FMBS (1 mg/kg) and spiperone (1 mg/kg) reduced [$^{18}F$]FMBS striatal-to-cerebellar ratio by 41% and 80%, respectively. (+)-Butaclamol (1 mg/kg) blocked 80% of the striatal [$^{18}F$]FMBS binding, while (-)-butaclamol (1 mg/kg) did not. Preinjection of SCH 23390 (1 mg/kg) and GBR 12909 (5 mg/kg) had no significant effect on [$^{18}F$]FMBS binding. Ketanserin (1 mg/kg), a ligand for the $5-HT_2$ receptors, did not cause significant inhibition either in striatum, in frontal cortex, or the remaining cortex. The results demonstrate that [$^{18}F$]FMBS labels DA $D_2$ receptors selectively in vivo in the mouse brain. It may hold promise as a selective radiotracer for studying DA $D_2$ receptors in vivo by PET.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.421-429
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• 2005

Purpose: It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with $[^{11}C]raclopride$. Materials and Methods: Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of $24.4{\pm}1.7$ years) were enrolled in this study $[^{11}C]raclopride$, a dopamine D2 receptor radioligand, was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes ($3{\times}20s,\;2{\times}60s,\;2{\times}120s,\;1{\times}180s\;and\;22{\times}300s$). following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar)/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. Results: The mean decrease in binding potential of $[^{11}C]raclopride$ between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7%, 4.0% and 7.8%, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, p=0.04). Conclusion: These data demonstrate that in vivo imaging with $[^{11}C]raclopride$ PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount or nicotine administered bt smoking.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.246-250
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• 2001

The dopamine D4 receptor gene has a hypervariable segment in the coding region characterized by a varying number of 48bp repeats in exon III of the gene. Varying the numbers of repeated segments may change the length, structure, and function of the receptor, which makes this gene a possible candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. We evaluated the dopamine D4 receptor genotype in male alcoholics and normal controls. All alcoholics and controls were unrelated and from the Korean population. Genotype and allele frequencies in 67 alcoholics were compared to 67 controls who were free of alcohol abuse, substance abuse, and major mental illness. No association was found between the dopamine D4 receptor allele and alcoholism. This result indicate that there is no association of the dopamine D4 receptor with alcoholism in Korean. Further systemized investigation to determine the role of dopamine D4 receptor gene in alcoholism with a larger sample size will be required.

• Korean Journal of Biological Psychiatry
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• v.19 no.1
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• pp.60-64
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• 2012

Objectives : This study was designed to investigate the association between the dopamine D2 receptor (DRD2) genetic polymorphism [TaqIB (rs17294542) and TaqID (rs1800498)] and patients with schizophrenia. Methods : TaqIB (rs17294542) and TaqID (rs1800498) polymorphism of the DRD2 gene were typed in 100 patients with schizophrenia and 109 normal controls. Results : There were no statistical differences in genotype and allele distribution of TaqIB (rs17294542) and TaqID (rs1800498) genetic polymorphism between patients with schizophrenia and normal controls. Conclusions : These results suggest that the TaqIB (rs17294542) and TaqID (rs1800498) polymorphisms of the DRD2 gene may not be associated with schizophrenia in the Korean population.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.225-233
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• 1997

The authors attempted to examine the allelic association between the A1 allele of Dopamine $D_2$ receptor and schizophrenia, alcoholism, drug addiction in Koreans. Schizophrenic patients(n=31), alcoholism(n=65), drug addiction(n=18) and controls(n=52) were examined by case-control study for distribution of the TaqI polymorphism of the dopamine $D_2$ receptor gene in Korean population to minimize the effect of racial differencies in gene frequencies. In schizophrenics, the numbers of schizophrenics with A1A1, A1A2, A2A2 were 9(29.0%), 15(48.4%) and 7(22.6%) respectively and in alcoholics with A1A1, A1A2, A2A2 were 14(21.5%), 36(55.4%) and 15(23.1%) respectively and in drug addiction with A1A1, A1A2, A2A2 were 2(11.1%), 10(55.6%) and 6(33.3%) respectively and in controls with A1A1, A1A2, A2A2 were 4(7.6%), 24(46.2%) and 24(46.2%) respectively. The prevalence of the A1 allele in schizophrenics, alcoholics, drug addiction and controls were 77%, 76.9%, 67% and 53.8% respectively. And the frequency of the A1 allele in schizophrenics, alcoholics, drug addiction and controls were 0.53, 0.49 0.39 and 0.31 respectively. There was significant difference in the frequency of the A1 allele between schizophrenics, alcoholics and controls. We also classified our alcoholic population. For classification by severity, we used the median MAST score 30 in our samples. There was also significant difference in the frequency of the A1 allele between less severe group(0.42) and more severe group(0.57). This data suggest that the A1 allele is associated with schizophrenia and alcoholism in Koreans. Furthermore the prevalence of the A1 allele increassed in more severely affected alcoholics. The authors conclude that our data support an allelic association between the A1 allele at dopamine $D_2$ receptor and schizophrenia, alcoholism. These results suggest the A1 allele of the $DRD_2$ gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.

• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.43-47
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• 1997

The author attempted to examine the allelic association between the A1 allele of Dopamine $D_2$ receptor and alcoholism in Koreans. The allelic distribution of Taq I polymorphism of the $D_2$ dopamine receptor gene with alcoholism was examined in 67 Korean alcoholics and compared with 100 Korean controls. In alcoholics, the numbers of alcoholics with A1A1, A1A2 and A2A2 were 11(16.4%), 30(44.8%) and 26(38.8%) respectively and in controls with A1A1, A1A2 and A2A2 were 17(17.0%), 42(42.0%) and 41(41.0%), respectively. The prevalence of the A1 allele in alcoholics was 61.2% and 59.0% in controls. And the frequency of the A1 allele in alcoholics and controls were 0.39 and 0.38, respectively. There was not significant difference in the frequency of the A1 allele between alcoholics and controls. This data suggest that the A1 allele is not associated with alcoholism in Koreans. The author conclude that our data do not support an allelic association between the A1 allele at Dopamine $D_2$ receptor and alcoholism. Further systemized studies will be necessary to determine whether the role of allele of Dopamine $D_2$receptor is major effect gene or modifying effect gene in the pathogenesis of alcoholism.

• Proceedings of the Ginseng society Conference
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• 1984.09a
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• pp.107-111
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• 1984

쥐의 뇌에서 추출한 입자상 아데닐산 고리화효소와 입자상 구아닐산효소의 활동성에 미치는 몇 가지 긴세노시드들의 효과를 조사하였다. $Rb_{2},\;Rb_{1}$, Rc 및 Re들과 같은 약간의 진세노사이드들이 두 효소들의 활동성을 상반적으로 변화시키는 것을 관찰하였다. 아데닐산 고리화효소와 구아닐산 고리화효소의 활동성에 미치는 GMP 및 AMP의 조절작용을 조사하였다. 긴세노시드 Rd로 방해된 아데닐산고리화효소는 GMP를 첨가함에 따라서 활성화되었다. 마찬가지로. 긴세노시드 $Rb_{2}$로 방해된 아데닐산 고리화효소도 GMP에 의해서 활성화되었다. 다른 한편, 긴세노시드 Rc로 활성화된 구아닐산 고리화효소는 AMP 또는 GMP를 첨가함에 따라서 방해되었다. 진세노사이드 $Rb_{2}$ 도파민 사이에는 아데닐산 고리화효소 계상의 수용체들에의 결함에 있어서 경쟁적이라는 것을 알았다. 이 결과는 긴세노시드 $Rb_{2}$가 세포의 D-1 도파민 수용체에 특이하게 결합한다는 것을 말해 준다.