BACKGROUND: Recent research demonstrates a strong association between smoking-related behaviors and genetic variation. We investigated the clinical features and genetic effects of dopamine receptors and a serotonin transporter on smoking cessation in Koreans. METHODS: Smokers (n=51) wanting to quit smoking were included as the study population. They were genotyped for polymorphisms in dopamine D2 receptor (DRD2) (TaqI and -141C), dopamine D4 receptor (DRD4), and a serotonin transporter (5-HTT). We defined abstinence as stopping smoking at six months after enrollment. RESULTS: Eighteen patients (35.3%) stopped smoking at six months. The abstinence group had a higher rate of alcohol use whereas the non-abstinence group had more coughing. However, there were no significant differences in average smoking rate, starting age of smoking, gender, nicotine dependence, and forced expiratory volume in one second between the two groups. As for the genes in the dopamine pathway, the polymorphisms of DRD2 TaqI (A1 allele) and DRD2 -141C (Ins C allele) were not genotypically different between the two groups (P=0.245 and 0.409, respectively). The genetic variation in the DRD4 variable number of tandem repeats (VNTR) also showed a similar distribution in the two groups. Regarding the polymorphisms of 5-HTT, there was no difference in the long allele between the two groups (P=0.852). CONCLUSIONS: This study suggests that the genetic variations of DRD2 TaqI, DRD2 -141C, DRD4 VNTR, and 5-HTT might have little influence on smoking cessation in Korean smokers.
Alleles ; Cough ; DNA ; Dopamine ; Forced Expiratory Volume ; Genetic Variation ; Humans ; Minisatellite Repeats ; Polymorphism, Genetic ; Receptors, Dopamine ; Receptors, Dopamine D2 ; Receptors, Dopamine D4 ; Serotonin Plasma Membrane Transport Proteins ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Use Disorder

We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.
Genotype ; Hand ; Humans ; Isoindoles ; Polymorphism, Genetic ; Real-Time Polymerase Chain Reaction ; Receptors, Dopamine ; Receptors, Dopamine D2 ; Receptors, Dopamine D4 ; Risperidone ; Schizophrenia ; Serotonin Plasma Membrane Transport Proteins ; Tandem Repeat Sequences ; Thiazoles

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 (4.5~8 Hz) and alpha (8~13 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.
Animals ; Apomorphine ; Benzazepines ; Dopamine ; Electroencephalography ; Haloperidol ; Rats ; Receptors, Dopamine ; Receptors, Dopamine D1 ; Receptors, Dopamine D2

A new structural polymorphism(Ser311 -> Cys311) in the dopamine D, receptor gene has been reported to be associated with schizophrenia, particularly in patients with a positive family history of schizophrenia. However these findings remain contorversial. Thus the authors investigated polymorphism of the dopamine D2 receptor gene(Ser311 -> Cys311) in a total of 136 Korean schizophrenic patients and 115 controls. Allele frequencies of Ser311 and Cys311 were determined by polymerase chain reaction(FCR) amplification of specific alleles according to Arinami and colleagues' method. The allele frequency of Cys311 in schizophrenic patients and controls was 0.011 and 0.017, respectively. There were no significant differencies in the allele frequency of Cys311 between schizophrenic patients and controls(x2=0.542, df=1, p>0.05). Neither schizophrenic patients nor controls were homozygous for Cys311. The authors findings contrasted with those of Arinami(1994), but were in line with results of previous studies(Asherson 1994 ; Laurent 1994 ; Nanko 1994b ; Nothen 1994: Sheikh 1994), which did not show evidence of association between schizophrenia and dopamine D2, receptor polymorphism(Ser311 -> Cys311).
Alleles ; Dopamine* ; Gene Frequency ; Humans ; Receptors, Dopamine D2* ; Schizophrenia

No abstract available.
Animals ; Apomorphine* ; Dopamine* ; Parkinsonian Disorders* ; Rats* ; Receptors, Dopamine D2*

OBJECTIVE: It has been suggested that the dopamine D2 receptor gene (DRD2) is associated with pathological gambling (PG). We investigated the association of the DRD2 Taq1A polymorphism and the temperament in PG using Cloninger's temperament and characteristic inventory (TCI). METHODS: 104 PG patients and 114 control subjects were recruited. Tests for DRD2 Taq1A polymorphism were conducted in both PG patients and controls. PG patients were requested to complete the TCI. RESULTS: There were no significant differences in frequencies of the genotype (chi2 = 0.77, p = 0.681), allele (chi2 = 0.52, p = 0.469), and allele (A1) carrier (chi2 = 0.15, p = 0.695) between the PG patients and the control group. When we compared the TCI profile in the PG patients according to genotypes, there were significant differences in harm-avoidance (HA, p = 0.033), and self-directedness (SD, p = 0.012) among genotypes. These difference were more evident between A1 allele carriers and non-carriers (HA, p = 0.009 and SD, p = 0.004). CONCLUSION: Present results suggest Taq1A polymorphism may not play an important role in the susceptibility to pathological gambling in our population. However, Taq1A polymorphism might be associated with some temperament in Korean PG patients.
Alleles ; Dopamine ; Gambling ; Genotype ; Humans ; Receptors, Dopamine D2 ; Temperament

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 D2 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 D2 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 (chi2(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.
Alleles ; Antipsychotic Agents* ; Dopamine Antagonists ; Dopamine* ; Humans ; Incidence ; Receptors, Dopamine ; Receptors, Dopamine D2* ; Retrospective Studies ; Schizophrenia

To determine the role of dopamine D2 receptor (D2R) in the nucleus accumbens (NAc) core in cocaine-induced behavioral sensitization, D2R antagonist, raclopride was bilaterally microinjected (2.5 or 5 nmol) into the NAc core of WT and D2R-/- mice and the initiation and expression phase of cocaine-mediated locomotor sensitization were analyzed. WT and D2R knockout (D2R-/-) mice received bilateral injections of either saline, or raclopride at the NAc core 30 min before each of five daily repeated injections of saline or cocaine (15 mg/kg i.p.). Following 2 weeks of withdrawal after repeated exposure to cocaine, the animals were pre-treated with an intra-accumbal injection of vehicle or raclopride before receiving a systemic cocaine challenge for the expression of sensitization. Animals which had been microinjected raclopride into NAc core displayed the enhancement of cocaine-induced behavioral response for the initiation but also for the expression of sensitization in WT as well as in D2R-/- mice, which was thus unaltered as compared to vehicle-injected control group. These results suggest that D2R in NAc core is not involved in cocaine-induced behavioral sensitization.
Animals ; Cocaine ; Dopamine ; Mice ; Microinjections ; Nucleus Accumbens ; Raclopride ; Receptors, Dopamine ; Receptors, Dopamine D2

The author attempted to allelic association between the a1 allele of Dopamine D2 receptor and alcoholism in Korean. The allelic disribution of Taq I polymorphism of the D2 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 control with A1A1, A1A2 and A2A2 were 17(17.0%), 42(42.0%), 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 on allelic association between the A1 allele at Dopamine D2 receptor and alcoholism. Further systemized studies will be necessary to determine whether the role of allele of Dopamine D2 receptor is major effect gene or modifying effect gene in the pathogenesis of alcoholism.
Alcoholics* ; Alcoholism ; Alleles ; Dopamine* ; Humans ; Prevalence ; Receptors, Dopamine ; Receptors, Dopamine D2

The results regarding an association between the polymorphism sites in the dopamine D1 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 D1 receptor gene in Korean popualtion to minimize the effect of racial differencies in gene frequencies. The frequencies of the B1 and B2 in schizophrenic patients were 0.11 and 9.89, respectively. And 0.10 and 0.90 in normal control. There was no significant differences in the frequencies in the allele B1 and 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 D1 receptor gene and Korean schizophrenic. The assumption that the dopamine D1 receptor gene has genetic role in the development of schizophrenia was not supported by this case-control study.
Alleles* ; Case-Control Studies ; Dopamine* ; Gene Frequency ; Humans ; Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Schizophrenia*