Influence of rs2587552 polymorphism of DRD2 gene on the effect of a childhood obesity intervention: A prospective, parallel-group controlled trial / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between rs2587552 polymorphism (has a strong lin-kage disequilibrium with rs1800497 which had been found in many studies to be related to obesity, r2=0.85) of DRD2 gene and the effect of a childhood obesity intervention in Chinese population, and provide a scientific basis for future personalized childhood obesity intervention based on genetic background.@*METHODS@#From a multi-center cluster randomized controlled trial studying the effect of a childhood obesity intervention, we enrolled 382 children from 8 primary schools (192 and 190 children from intervention and control groups, respectively) in Beijing as study subjects. Saliva was collected and DNA was extracted to detect the rs2587552 polymorphism of DRD2 gene, and the interactions between the gene and study arms on childhood obesity indicators [including body weight, body mass index (BMI), BMI Z-score, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, and body fat percentage] were analyzed.@*RESULTS@#No association was found between rs2587552 polymorphism and the changes in hip circumference or body fat percentage in the intervention group (P>0.05). However, in the control group, children carrying the A allele at DRD2 rs2587552 locus showed a greater increase in hip circumference and body fat percentage compared with those not carrying A allele (P < 0.001). There were interactions between rs2587552 polymorphism of DRD2 gene and study arms on the changes in hip circumference and body fat percentage (P=0.007 and 0.015, respectively). Compared with the control group, children in the intervention group carrying the A allele at DRD2 rs2587552 locus showed decrease in hip circumference by (-1.30 cm, 95%CI: -2.25 to -0.35, P=0.007) and decrease in body fat percentage by (-1.34%, 95%CI: -2.42 to -0.27, P=0.015) compared with those not carrying A allele. The results were consistent between the dominant model and the additive model (hip circumfe-rence: -0.66 cm, 95%CI: -1.28 to -0.03, P=0.041; body fat percentage: -0.69%, 95%CI: -1.40 to 0.02, P=0.056). No interaction was found between rs2587552 polymorphism and study arms on the changes in other childhood obesity-related indicators (P>0.05).@*CONCLUSION@#Children carrying the A allele at rs2587552 polymorphism of DRD2 gene are more sensitive to intervention and showed more improvement in hip circumference and body fat percentage after the intervention, suggesting that future personalized childhood obesity lifestyle intervention can be carried out based on the rs2587552 polymorphism of DRD2 gene.

No association between dopamine D2 receptor (DRD2) alleles and crack/cocaine dependence in Brazilians

INTRODUCTION: The causal mechanisms behind crack/cocaine use are still unknown, but genetic influences are suggested. OBJECTIVE: To investigate the relationship between the genetic polymorphism TaqI (rs1800497) in the dopamine D2 receptor (DRD2) gene and susceptibility to crack/cocaine dependence in a group of addicts to crack/cocaine and a non-addicted group. METHODS: The case group (n=515) was composed of crack/cocaine-dependent men and the control group (n=106) comprised men who were considered not dependent on crack/cocaine. The oral hygiene habits, decayed, missing, and filled teeth index, gingival index, and plaque index were evaluated. The reference single nucleotide polymorphism (rs1800497 C/T) of the DRD2 gene was genotyped by a real-time polymerase chain reaction technique. Student's t-tests for independent samples or the non-parametric Mann-Whitney test were used to compare groups regarding quantitative variables. RESULTS: The case group showed a mean time of 9.91±7.03 years of crack use, and 61.06±92.96 stones/week. The socio-demographic profile of the sample was White, single men, with basic education, blue-collar worker, smoker, and reporting alcohol use. There was a high frequency of gingival inflammation, plaque accumulation, and caries experience. For all genetic models tested, there was no significant difference in the genotypic frequency in rs1800497 of the DRD2 gene, between case and control groups (p>0.05). CONCLUSION: The genetic variant in the DRD2 did not increase the vulnerability to develop crack/cocaine dependence. The complex genetic nature of crack/cocaine dependence and a large variation of DRD2 allele frequencies, depending on the population group sampled, could be one explanation for the no association.

Long-term Effects of Aripiprazole Treatment during Adolescence on Cognitive Function and Dopamine D2 Receptor Expression in Neurodevelopmentally Normal Rats

OBJECTIVE: This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats. METHODS: Adolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36–56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71–84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis. RESULTS: Spontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed significantly among the 3 groups (F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group (post-hoc test p = 0.013). D2R levels in the medial PFC (F = 8.72, p = 0.001) and hippocampus (F = 13.54, p < 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risperidone-treated rats (post-hoc test p = 0.025 and p < 0.001, respectively) and controls (post-hoc test p < 0.001, all). CONCLUSION: This study showed that aripiprazole treatment in adolescence could influence cognitive function and dopaminergic neurotransmission into early adulthood.

Dopamine D2 receptor may be involved in the regulation of cortical-striatum synaptic transmission and autonomic activity in PD mice by exercise / 生理学报

The aim of the present study was to reveal the role of cortical-striatum postsynaptic dopamine D2 receptor (D2R) in improving motor behavioral dysfunction in Parkinson's disease (PD) mice by exercise. C57/BL6 male adult mice were randomly divided into control, PD and PD plus exercise groups. The mice were injected with 6-OHDA in striatum to establish a unilateral injury PD model. The exercise intervention program was uniform speed running (16 m/min, 40 min/d, 5 d per week for 4 weeks). Autonomic activity of mice was tested by open field test. Cortical-striatum synaptic transmission efficiency was assessed by peak amplitude of field excitatory postsynaptic potential (fEPSP) recorded from in vitro brain slides. Meanwhile, the effects of D2R agonist on autonomic activity and cortical-striatal synaptic transmission were observed. The results showed that, compared with PD group, PD plus exercise group exhibited significantly increased autonomic motor distance and proportion of fast-moving (P < 0.05), as well as decreased maximum amplitude of fEPSP under increasing stimulation intensity (0.75-3.00 pA) (P < 0.05) and slope of stimulus-response curve. Compared with PD mice without D2R agonist, the movement distance and rapid movement ratio of PD mice treated with D2R agonist were increased significantly (P < 0.05), whereas fEPSP peak amplitude (P < 0.05) and the slope of stimulus-response curve were decreased. These results indicate that either early exercise intervention or D2R agonist treatment can inhibit the abnormal increase of cortical-striatum synaptic transmission and improve the autonomic motor ability in PD mice, suggesting that the cortical-striatum synaptic D2R may be an important molecular target for exercise to improve the autonomic motor ability of PD mice.

Role of Helix 8 in Dopamine Receptor Signaling

G protein-coupled receptors (GPCRs) are membrane receptors whose agonist-induced dynamic conformational changes trigger heterotrimeric G protein activation, followed by GRK-mediated phosphorylation and arrestin-mediated desensitization. Cytosolic regions of GPCRs have been studied extensively because they are direct contact sites with G proteins, GRKs, and arrestins. Among various cytosolic regions, the role of helix 8 is least understood, although a few studies have suggested that it is involved in G protein activation, receptor localization, and/or internalization. In the present study, we investigated the role of helix 8 in dopamine receptor signaling focusing on dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R). D1R couples exclusively to Gs, whereas D2R couples exclusively to Gi. Bioinformatic analysis implied that the sequences of helix 8 may affect GPCR-G protein coupling selectivity; therefore, we evaluated if swapping helix 8 between D1R and D2R changed G protein selectivity. Our results suggest that helix 8 is not involved in D1R-Gs or D2R-Gi coupling selectivity. Instead, we observed that D1R with D2R helix 8 or D1R with an increased number of hydrophobic residues in helix 8 relative to wild-type showed diminished β-arrestin-mediated desensitization, resulting in increased Gs signaling.

Prevalence of polymorphisms in the ANKK1, DRD2, DRD3 genes and metabolic syndrome in refractory schizophrenia / Prevalência de polimorfismos nos genes ANKK1, DRD2, DRD3 e síndrome metabólica na esquizofrenia refratária / Prevalencia de polimorfismos en los genes ANKK1, DRD2, DRD3 y síndrome metabólico en la esquizofrenia refractária

ABSTRACT Objective: to estimate the prevalence of TaqIA, -141C and rs6280 polymorphisms of the ANKK1, DRD2 and DRD3 genes and evaluate their association with the occurrence of metabolic syndrome in patients with refractory schizophrenia. Method: cross-sectional study conducted in the Extended Western Region of Minas Gerais, with refractory schizophrenic patients using the antipsychotic clozapine. Sociodemographic, clinical, anthropometric, biochemical and genetic data were collected. Univariate analysis of the data was performed. Results: seventy-two patients participated in the study and the occurrence of Metabolic Syndrome was observed in 47.2% of them. There was no association between Metabolic Syndrome and the studied polymorphisms. There was a statistically significant difference in the low HDL parameter with homozygous genotype for the C allele of the -141C polymorphism of the DRD2 gene. Conclusion: a high prevalence of MS was evidenced. The -141C polymorphism was associated with low HDL. Genetic analysis and identification of metabolic alterations in this group of patients can guide drug treatment and provide a better quality of life.

RESUMO Objetivo: estimar a prevalência dos polimorfismos TaqIA, -141C e rs6280 dos genes ANKK1, DRD2 e DRD3 e avaliar sua associação com a ocorrência de síndrome metabólica em pacientes com esquizofrenia refratária. Método: estudo de delineamento transversal, realizado na Região Ampliada Oeste de Minas Gerais, que incluiu pacientes com esquizofrenia refratária em uso do antipsicótico clozapina. Foram coletados dados sociodemográficos, clínicos, antropométricos, bioquímicos e genéticos. Realizou-se análise univariada dos dados. Resultados: participaram 72 pacientes e observou-se a ocorrência de Síndrome Metabólica em 47,2%, não sendo encontrada associação da Síndrome Metabólica com os polimorfismos estudados. Houve diferença estatisticamente significante com o parâmetro do baixo HDL com genótipo homozigoto para alelo C do polimorfismo -141C do gene DRD2. Conclusão: evidenciou-se prevalência de SM elevada. O polimorfismo -141C associou-se ao baixo HDL. A análise genética e a identificação de alterações metabólicas, neste grupo de pacientes, podem nortear o tratamento medicamentoso e propiciar melhor qualidade de vida.

RESUMEN Objetivo: estimar la prevalencia de los polimorfismos TaqIA, -141C y rs6280 de los genes ANKK1, DRD2 y DRD3 y evaluar su asociación con el síndrome metabólico en pacientes con esquizofrenia refractária. Método: estudio de delineamiento transversal, realizado en la Región Ampliada Oeste de Minas Gerais, que incluye pacientes con esquizofrenia refractária usando el antipsicótico clozapina. Fueron recogidos datos sociodemográficos, clínicos, antropométricos, bioquímicos y genéticos. Se realizó um análisis univariada de los datos. Resultados: participaron 72 pacientes y se observó el Síndrome Metabólico en 47,2%, no siendo encontrada una asociación del Síndrome Metabólico con los polimorfismos estudiados. Hubo diferencia estadísticamente significante con el parámetro del bajo HDL con genotipo homozigoto para alelo C del polimorfismo -141C del gen DRD2. Conclusión: se vio una prevalencia de SM elevada. El polimorfismo -141C se asoció al bajo HDL. El análisis genético y la identificación de alteraciones metabólicas, en este grupo de pacientes, pueden guiar al tratamiento medicamentoso y propiciar mejor calidad de vida.

Polimorfismos del receptor D2 / D2 receptor polymorphisms

Los prolactinomas son tumores bien diferenciados que se originan en las células lactotropas pituitarias, una línea celular que secreta fisiológicamente prolactina (PRL). A nivel hipofisario, la dopamina está implicada en la regulación de la secreción de PRL por las células lactotropas y este efecto inhibitorio está mediado por la activación del receptor de prolactina tipo 2 (DRD2). Hay varios polimorfismos del DRD2, el primero y más estudiado es TaqI A1; está demostrado que este alelo se encuentra asociado a una reducción de la actividad cerebral dopaminérgica, además de observarse una reducción en su capacidad de unión de aproximadamente un 30%. Este alelo se ha vinculado con una menor densidad de DRD2 en el cuerpo estriado, especialmente en el putamen y caudado ventral, y la cantidad de DRD2 en portadores del alelo A1 fue un 30-40% más bajo que en los no portadores (es decir, TaqI A2 homocigotos). En la literatura, hay evidencia que apoya la posible participación de los polimorfismos DRD2 en la regulación de la secreción hormonal.

Prolactinomas are well differentiated tumours that originate in the pituitary lactotrope cells, a cell line that physiologically secretes prolactin (PRL). At pituitary level, dopamine is involved in the regulation of PRL secretion by lactotropes, and this inhibitory effect is mediated by activation of prolactin type 2 receptor (DRD2). Of the several DRD2 polymorphisms, the first and most studied is TaqI A1. It has been demonstrated that this allele is associated with a reduced dopaminergic brain activity, and a reduction in its binding capacity of approximately 30% also being observed. This allele was associated with a lower density of DRD2 in the striatum, especially in the putamen and ventral caudate. The amount of DRD2 in A1 allele carriers was 30 - 40% lower than in non-carriers (this is, TaqI A2 Homozygotes). There is evidence in the literature, that supports the possible involvement of DRD2 polymorphisms in the regulation of hormonal secretion.

The Relationship between the Amisulpride-Induced Hyperprolactinemia and Taq1A Polymorphism of the Dopamine D2 Receptor Gene in Schizophrenia Patients

OBJECTIVES: This study was aimed to investigate the association between amisulpride-induced hyperprolactinemia and the Taq1A polymorphism in the D2 dopamine receptor gene (DRD2) in schizophrenic patients. METHODS: The plasma concentrations of prolactin were measured before and after treatment with amisulpride in one hundred and twenty-five schizophrenic patients. The effect of the Taq1A variants of the DRD2 on the risk of amisulpride-induced hyperprolac-tinemia was the main the outcome measure. The genotyping for Taq1A (rs1800497) polymorphism was performed using TaqMan single nucleotide polymorphism (SNP) genotyping assay. RESULTS: There was a significant difference between the prolactin level at baseline and the 6th week after treatment with amisulpride in all the subjects. However, there were no significant correlations between ΔProlactin (the difference between prolactin level at baseline and the 6th week after treatment) and the Taq1A genotypes. CONCLUSIONS: This is the first study to investigate the-correlations between the Taq1A polymorphism and the amisulpride-induced hyperprolactinemia in Korean schizophrenic patients. The current results suggested the further large-scale researches on various SNPs in the DRD2 gene will establish clear goals and provide answers to the unanswered questions described in this study.

Reduction of Severity of Recurrent Psychotic Episode by Sustained Treatment with Aripiprazole in a Schizophrenic Patient with Dopamine Supersensitivity: A Case Report

Dopamine supersensitivity psychosis (DSP) is a type of acute exacerbation of recurrent psychosis caused by long-term treatment with antipsychotics in schizophrenic patients. Although DSP is exceedingly troublesome for clinicians, effective treatment has not yet been established. Based on clinical research and our animal study, we hypothesize that aripiprazole, an atypical anti-psychotic, may reduce the exacerbation of recurrent psychotic episodes. We report the case of a 46-year-old female who suffered from schizophrenia with DSP. In this case, sustained treatment with a high dose of aripiprazole gradually reduced the severity of her recurrent psychotic episodes. In conclusion, sustained treatment with aripiprazole may reduce the exacerbation of recurrent psychotic episodes in schizophrenic patients with DSP, and may be an effective treatment of DSP.

Inhibition of SKP2 Sensitizes Bromocriptine-Induced Apoptosis in Human Prolactinoma Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most common estrogen-related functional pituitary tumors. As an agonist of the dopamine D2 receptor, bromocriptine is used widely to inhibit prolactinoma progression. On the other hand, it is not always effective in clinical application. Although a dopamine D2 receptor deficiency contributes to the impaired efficiency of bromocriptine therapy to some extent, it is unknown whether there some other underlying mechanisms leading to bromocriptine resistance in prolactinoma treatment. That is the main point addressed in this project. MATERIALS AND METHODS: Human prolactinoma samples were used to analyze the S-phase kinase associated protein 2 (SKP2) expression level. Nutlin-3/adriamycin/cisplatin-treated GH3 and MMQ cells were used to analyze apoptosis in SKP2 overexpression or knockdown cells. SKP2 expression and the interaction partners of SKP2 were also detected after a bromocriptine treatment in 293T. Apoptosis was analyzed in C25 and bromocriptine-treated GH3 cells. RESULTS: Compared to normal pituitary samples, most prolactinoma samples exhibit higher levels of SKP2 expression, which could inhibit apoptosis in a p53-dependent manner. In addition, the bromocriptine treatment prolonged the half-life of SKP2 and resulted in SKP2 overexpression to a greater extent, which in turn compromised its pro-apoptotic effect. As a result, the bromocriptine treatment combined with C25 (a SKP2 inhibitor) led to the maximal apoptosis of human prolactinoma cells. CONCLUSION: These findings indicated that SKP2 inhibition sensitized the prolactinoma cells to bromocriptine and helped promote apoptosis. Moreover, a combined treatment of bromocriptine and C25 may contribute to the maximal apoptosis of human prolactinoma cells.

Direct modulation of firing activity by dopamine Dlike receptors in the globus pallidus of both normal and parkinsonian rats / 生理学报

The globus pallidus occupies a critical position in the indirect pathway of the basal ganglia circuit, which regulates movement under both normal and pathological conditions. Previous studies have shown that the globus pallidus receives dopaminergic innervation from the axonal collaterals of nigrostriatal fibers. Both dopamine Dand Dlike receptors are expressed in the globus pallidus. The present study was aimed to investigate the direct in vivo electrophysiological effects of dopamine Dlike receptors in the globus pallidus of both normal and parkinsonian rats. Extracellular recordings of multi-barreled microelectrode were used in the present study. In normal rats, micro-pressure ejection of dopamine Dlike receptor agonist quinpirole induced different effects on the firing rate of globus pallidus neurons. In 24 out of the 61 pallidal neurons, quinpirole significantly increased the firing rate by (62.7 ± 11.2)%. In another 16 neurons, quinpirole decreased the spontaneous firing rate by (37.5 ± 2.9)%. Furthermore, co-application of dopamine Dlike receptor antagonist, sulpride, blocked quinpirole-induced modulation of the firing rate of pallidal neurons. On the 6-hydroxydopamine (6-OHDA) lesioned side of parkinsonian rats, quinpirole increased the firing rate in 25 out of the 47 pallidal neurons by (64.2 ± 10.1)%, while decreased the firing rate in 11 neurons by (51.9 ± 6.2)%. Our findings suggest that activation of pallidal dopamine Dlike receptors may bidirectionally modulate the spontaneous firing of globus pallidus neurons in both normal and parkinsonian rats.

mRNA expression of dopamine receptor D2 and dopamine transporter in peripheral blood lymphocytes before and after treatment in children with tic disorder / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the mRNA expression of dopamine receptor D2 (DRD2) and dopamine transporter (DAT) in peripheral blood lymphocytes before and after treatment in children with tic disorder (TD).</p><p><b>METHODS</b>RT-PCR was used to measure the mRNA expression of DRD2 and DAT in peripheral blood lymphocytes before and after treatment in 60 children with TD. The correlations between mRNA expression of DRD2 and DAT and the severity of TD were analyzed. Sixty healthy children served as the control group.</p><p><b>RESULTS</b>Before treatment, the children with TD had a significant increase in the mRNA expression of DRD2 and DAT compared with the control group (P<0.05). After 3 months of treatment with oral aripiprazole, the mRNA expression of DRD2 decreased significantly (P<0.05), while that of DAT showed no significant changes in children with TD. In the children with moderate or severe TD, the mRNA expression of DRD2 was positively correlated with Yale Global Tic Severity Scale (YGTSS) score (P<0.05). In the children with moderate TD, the mRNA expression of DAT was positively correlated with YGTSS score (P<0.05).</p><p><b>CONCLUSIONS</b>In children with TD, the mRNA expression of DRD2 in peripheral blood lymphocytes can be used as one of the indicators for diagnosing TD, assessing the severity of TD, and evaluating clinical outcomes.</p>

Effects of rs4274224 polymorphisms in the DRD2 gene and family factors on the regularity based on the temperament in school-age children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of rs4274224 polymorphisms in the DRD2 gene, family factors and their interaction on the regularity in school-age children.</p><p><b>METHODS</b>The rs4274224 polymorphisms were genotyped using Sequenom Mass Array. The regularity was assessed based on the Middle Childhood Temperament Questionnaire (MCTQ). The parental rearing pattern was assessed with Egna Minnen av Bardnodnauppforstran (EMBU). The family function was assessed using Family Cohesion and Adaptability Scale (FACES II-CV).</p><p><b>RESULTS</b>The regularity score in children with AA genotype of rs4274224 in the DRD2 gene was significantly lower than in those with GA/GG genotype (2.9±0.6 vs 3.1±0.7; P<0.05). The results of multiple regression analysis showed that the regularity was related to child gender, father's education level and family adaptability. The results of logistic regression analysis showed that the main factors influencing the regularity were family adaptability and its interaction with rs4274224 polymorphisms. The regularity was better in children with high family adaptability than in those with low family adaptability (OR=0.112, P<0.01). The children with AA genotype and low family adaptability were tend to be associated with low regularity (OR=21.554, P<0.01).</p><p><b>CONCLUSIONS</b>The regularity based the temperament for school-age children might be influenced by family adaptability and its interaction with rs4274224 polymorphisms.</p>

Association of D2 dopamine receptor gene -141C Ins/Del polymorphisms with heroin dependence in Chinese Han population: a meta-analysis / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the association between D2 dopamine receptor gene -141C Ins/Del polymorphism and heroin dependence in Chinese Han population.@*METHODS@#Chinese and foreign databases were searched for relevant articles published from the establishment of database to March 2014. Case-control studies on D2 dopamine receptor gene -141C Ins/Del polymorphism with heroin dependence in Chinese Han population were gathered with Meta-analysis by Stata 12.0 software after data abstraction.@*RESULTS@#Seven case-control studies on association between D2 dopamine receptor gene -141C Ins/ Del polymorphism and heroin dependence were included, which covered 3 211 heroin dependence patients and 1 979 controls. Meta-analysis results showed that the pooled odds ratio (OR), the 95% confidence interval (CI) and P value after combining genotypes were as follows: Ins/Ins vs Del/Del: OR=0.51, 95% CI: 0.27-0.96, P=0.017; Ins/Ins vs Ins/Del+Del/Del: OR=0.82, 95% CI: 0.72-0.94, P=0.448; Ins/Ins+ Ins/Del vs Del/Del: OR=0.53, 95% CI: 0.28-0.98, P=0.019; Ins/Del vs Del/Del: OR=0.59, 95% CI: 0.32-1.07, P=0.045; Ins vs Del: OR=0.79, 95% CI: 0.71-0.89, P=0.101).@*CONCLUSION@#D2 dopamine receptor gene -141C Ins/Del polymorphism is associated with heroin dependence in Chinese Han population, and Chinese Han population with Ins allele gene deletion are at lower risk of heroin dependence.

Association between rs1079595 polymorphisms in the DRD2 gene and the distractibility based the temperament in school-age children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the association between rs1079595 polymorphisms in the DRD2 gene and the distractibility in school-age children.</p><p><b>METHODS</b>The genotyping at rs1079595 was performed and the distractibility was measured based on the temperament questionnaire in 120 8-12 years old school-age children in order to analyze the effects of the rs1079595 polymorphism and its interaction with the gender, age and delivery mode on the distractibility.</p><p><b>RESULTS</b>There was an association between the distractibility and rs1079595 polymorphisms. The distractibility score in children with GG/GT genotypes was significantly higher than in children with the TT genotype (4.3 ± 0.6 vs 4.0 ± 0.7; P<0.05). The interaction between rs1079595 polymorphisms and the delivery mode produced an effect on the distractibility. The normal delivery children with T alleles were associated with a low distractibility (OR=0.037, P<0.01).</p><p><b>CONCLUSIONS</b>The distractibility based the temperament might be influenced by the rs1079595 polymorphism and its interaction with the delivery mode in school-age children.</p>

Melanocortin 4 Receptor and Dopamine D2 Receptor Expression in Brain Areas Involved in Food Intake

BACKGROUND: The melanocortin 4 receptor (MC4R) is involved in the regulation of homeostatic energy balance by the hypothalamus. Recent reports showed that MC4R can also control the motivation for food in association with a brain reward system, such as dopamine. We investigated the expression levels of MC4R and the dopamine D2 receptor (D2R), which is known to be related to food rewards, in both the hypothalamus and brain regions involved in food rewards. METHODS: We examined the expression levels of D2R and MC4R by dual immunofluorescence histochemistry in hypothalamic regions and in the bed nucleus of the stria terminalis (BNST), the central amygdala, and the ventral tegmental area of transgenic mice expressing enhanced green fluorescent protein under the control of the D2R gene. RESULTS: In the hypothalamic area, significant coexpression of MC4R and D2R was observed in the arcuate nucleus. We observed a significant coexpression of D2R and MC4R in the BNST, which has been suggested to be an important site for food reward. CONCLUSION: We suggest that MC4R and D2R function in the hypothalamus for control of energy homeostasis and that within the brain regions related with rewards, such as the BNST, the melanocortin system works synergistically with dopamine for the integration of food motivation in the control of feeding behaviors.

Distribution of D1 and D2-dopamine receptors in calcium-binding-protein expressing interneurons in rat anterior cingulate cortex / 生理学报

Dopamine plays an important role in cognitive functions including decision making, attention, learning and memory in the anterior cingulate cortex (ACC). However, little is known about dopamine receptors (DAR) expression patterns in ACC neurons, especially GABAergic interneurons. The aim of the present study was to investigate the expression of the most abundant DAR subtypes, D1 receptors (D1Rs) and D2 receptors (D2Rs), in major types of GABAergic interneurons in rat ACC, including parvalbumin (PV)-, calretinin (CR)-, and calbindin D-28k (CB)-containing interneurons. Double immunofluorescence staining and confocal scanning were used to detect protein expression in rat brain sections. The results showed a high proportion of PV-containing interneurons express D1Rs and D2Rs, while a low proportion of CR-positive interneurons express D1Rs and D2Rs. D1R- and D2R-expressing PV interneurons are more prevalently distributed in deep layers than superficial layers of ACC. Moreover, we found the proportion of D2Rs expressed in CR cells is much greater than that of D1Rs. These regional and interneuron type-specific differences of D1Rs and D2Rs indicate functionally distinct roles for dopamine in modulating ACC activities via stimulating D1Rs and D2Rs.

The effects of DR2 on myocardial ischemic postconditioning and its underlying mechanisms / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effects of dopamin receptors-2 (DR2) on myocardial ischemic postconditioning and explore its underlying mechanisms.</p><p><b>METHODS</b>The myocardial ischemic postconditioning (PC) model was established in cultured primary rat neonatal cardiomyocytes which were then randomly assigned in the following groups: Nomial control group, Isehemia/reperfusion (L'R) group, PC (ischemic postconditioning) group, PC + Bro (Bromocriptine, a DB2 antagonist) group, PC + Hal (Haloperidol, a DB2 repressor) and PC + Hal + Bro groups. The lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in cell medium were analyzed by colorunetry. The cell ultrastructure changes were observed by transmission electron microscope. The cell apoptosis was analyzed using flowcytometiy. The protein expression level of D112 and activity of p-p38 and p-JNK were detected by Western blot.</p><p><b>RESULTS</b>Compared with the nonnal control group, hR increased the protein expression level of DB2, enhanced LDH activity and MDA content, promoted cell injury and apoptosis, decreased SOD activity, up-regulated the activity of p-p38 and p-JNK. Compared with the hR group, although PC further increased the expression of DR2 protein, it decreased LDH activity and MDA content, cell injury and apoptosis, increased SOD activity, down-regulated activity of p-p38 and p-JNK. Bromocriptine treatment further enhanced PC-induced canlioprotective effect, yet Hal addition attenuated this enhancing effect exerted by bromocriptine.</p><p><b>CONCLUSION</b>The activation of DB2 is involved in the protective effect of ischemic postconditioning on myocardial ischemia/reperfusion injury through down-regulating the activity of p-p38 and p-JNK.</p>

Late-onset Quetiapine-related Tardive Dyskinesia Side Effects in a Patient with Psychotic Depression

The atypical antipsychotics were believed to induce less extrapyramidal syndrome, including tardive dyskinesia (TD). Since the introduction of the quetiapine, it is also reported with less TD side effects. It even can relieve the symptoms of severe TD and reduce the risk of TD. The quetiapine's low affinity and fast dissociation from postsynaptic dopamine D2 receptors should give the least risk of producing the symptoms of TD. The quetiapine even can reduce the TD side effects related to clozapine, which has the lowest risk for TD. However, since the first case report of TD side effects related to quetiapine published on 1999, the safety of quetiapine in TD aspect has been questioned. Therefore, we want to share this case report, which was written to describe the severe late-onset TD side effects after long-term use of quetiapine in a patient with psychotic depression. The patient had no significant findings after concurrent comprehensive neurological examinations, magnetic resonance imaging of brain and electroencephalogram since the onset of TD.

Trial of Metoclopramide on Oro-facial Dyskinesia Following Traumatic Brain Injury: A Case Report

Oro-facial dyskinesia is characterized by involuntary repetitive movements of the tongue, lip, or jaw, which is known to be derived by variable causes. Pre- and post-synaptic dopamine receptor abnormalities by degenerative changes in the brain seem to be the key pathophysiology, but the exact mechanism still remained to be unknown. Metoclopramide can pass the blood-brain barrier, which is known for a selective presynaptic autoregulating dopamine D2 receptor antagonist in the brain, and is usually prescribed for dyspepsia, nausea and vomiting. In particular, it was also reported to improve the symptoms of diurnal bruxism after brain injury. With reviewing some of literatures, we present a case of 27 year old man with traumatic brain injury who showed improvement of oro-facial dyskinesia after taking oral metoclopramide.