No abstract available.
Dopamine* ; Parkinson Disease* ; Receptors, Dopamine*

Desensitization and acute tolerance are terms used to describe the attenuation of receptor responsiveness by prolonged or intermittent exposure to an agonist. Unlike desensitization of G protein-coupled receptors (GPCRs), which is commonly explained by steric hindrance caused by the β-arrestins that are translocated to the activated receptors, molecular mechanisms involved in the acute tolerance of GPCRs remain unclear. Our studies with several GPCRs and related mutants showed that the acute tolerance of GPCRs could occur independently of agonist-induced β-arrestin translocation. A series of co-immunoprecipitation experiments revealed a correlation between receptor tolerance and interactions among receptors, β-arrestin2, and Gβγ. Gβγ displayed a stable interaction with receptors and β-arrestin2 in cells expressing GPCRs that were prone to undergo tolerance compared to the GPCRs that were resistant to acute tolerance. Strengthening the interaction between Gβγ and β-arrestin rendered the GPCRs to acquire the tendency of acute tolerance. Overall, stable interaction between the receptor and Gβγ complex is required for the formation of a complex with β-arrestin, and determines the potential of a particular GPCR to undergo acute tolerance. Rather than turning off the signal, β-arrestins seem to contribute on continuous signaling when they are in the context of complex with receptor and Gβγ.
Immunoprecipitation ; Receptors, Dopamine D3

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

OBJECTIVES: We investigated the relationship of personality traits with dopamine D4 receptor(DRD4) exon III polymorphism in a Korean population. METHODS: We analysed DRD4 exon III 48-bp repeats polymorphism in 173 Korean healthy female adolescents(age=13.88+/-0.29 years) who also completed Temperament and Character Inventory(TCI). RESULTS: Novelty seeking score of the TCI was significantly higher in the subjects with DRD4 long alleles(>or=5 repeats) compared with the subjects without these(t=2.11, p=0.037). CONCLUSION: The present study supports the previous reports that long repeats of the DRD4-exon III polymorphism are related with Novelty Seeking personality.
Dopamine* ; Exons ; Female ; Humans ; Receptors, Dopamine* ; 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

BACKGROUND: Dopamine receptors are strong candidates for involvement in schizophrenia and are target of a wide variety of antipsychotics. Dopamine D5 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 D5 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 resonse to antipsychotic. RESULT: DRD5 polymorphism was not associated with treatment response to a variety of antipsychotics in chronic schizophrenic patients. CONCLUSION: Genetic variation of D5 receptors do not predict treatment response to antispychotics.
Antipsychotic Agents ; Dopamine* ; Genetic Variation ; Genotype* ; Humans ; Polymerase Chain Reaction ; Receptors, Dopamine ; Receptors, Dopamine D5* ; Schizophrenia

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*

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