Dopamine D2 Receptor Gene Research Articles

Association of dopamine receptor D2 gene (DRD2) Taq1 polymorphisms with eating behaviors and obesity among Chinese and Indian Malaysian university students.

This study investigated the association of DRD2 Taq1A, Taq1B and Taq1D gene polymorphisms with eating behavior, the preference/intake frequency/craving of high-fat foods and obesity in 394 Malaysian adults (161 males, 233 females; 308 Chinese, 86 Indians; 67 obese, 327 non-obese). Eating behaviors namely Cognitive Restraint, Uncontrolled Eating and Emotional Eating scores were assessed by the Three Factor Eating Questionnaire-R18. The preference/intake frequency/craving of 26 common high-fat Malaysian foods was assessed using a 7-point hedonic scale. Anthropometric measurements were taken and Taq1 gene polymorphisms were genotyped by PCR-Restriction Fragment Length Polymorphism using DNA extracted from mouthwash samples. The overall minor allele frequencies of Taq1A, Taq1B and Taq1D according to ethnicities (Chinese/Indian) were 0.37/0.29, 0.39/0.28, 0.06/0.30, respectively; genotype and allele distributions of Taq1B and Taq1D were significantly different between ethnicities. Eating behaviorscores were not significantly different between gender and ethnicities. Those with A1 or B1 allele had lower Cognitive Restraint score and higher Uncontrolled Eating score, while those with A1/A1 or B1/B1 genotype had higher fast food preference. D1 allele was associated with increased starchy food craving and mamak (Malaysian Indian-Muslim) food preference, but not eating behavior scores. All three gene variants were not associated with obesity and adiposity. Taken together, we posit that three DRD2 Taq1 gene polymorphisms influence the eating behavior and preference/intake frequency/craving of certain high-fat foods in Malaysian adults, but their role in obesity and adiposity is still inconclusive and needs further investigation.

Effects of ammonia-N exposure on the concentrations of neurotransmitters, hemocyte intracellular signaling pathways and immune responses in white shrimp Litopenaeus vannamei

The effects of ammonia-N exposure (transferred from 0.07 to 2, 10 and 20 mg L−1) on the mechanism of neuroendocrine-immunoregulatory network were investigated in Litopenaeus vannamei. The results showed that biogenic amines (dopamine, noradrenaline, 5-hydroxytryptamine) concentrations in treatment groups increased significantly within 12 h. The gene expression of guanylyl cyclase increased significantly from 3 h to 24 h. And dopamine receptor D4 and α2 adrenergic receptor gene expression in treatment groups decreased significantly within 12 h, whereas the mRNA expression of 5-HT7 receptor increased significantly within 3 h and reached the peak levels at 6 h. The second messengers (cAMP, cGMP) and Calmodulin (CaM) increased significantly in treatment groups after 3 h. The concentrations of protein kinases (PKA, PKG) shared a similar trend in cAMP and cGMP which were up-regulated and reached the peak value at 6 h, while the PKC decreased within 3 h and arrived at its bottom at 6 h. The nuclear factor kappa-b and cAMP-response element binding protein mRNA expression levels of treatment shrimps increased sharply and reached maximum values at 6 h. The total hemocyte count, phagocytic activity, antibacterial activity in treatment groups decreased dramatically within 48 h. Whereas the phenoloxidase activities slightly up-regulated. Then it was decreased significantly up to 48 h. α2-macroglobulin activity decreased at the first 3 h-stress. Then they up-regulated significantly in 6 h. The results suggest that there are two crucial neuroendocrine substances (biogenic amine and CHH), which play a principal role in adapting to ammonia-N exposure and cause immune response through cAMP-, CaM- and cGMP-dependent pathways.

Examining the Impact of Maternal Individual Features on Children's Behavioral Problems in Adoptive Families: The Role of Maternal Temperament and Neurobiological Markers.

The first year after adoption constitutes a sensitive period for both strengthening the new emotional bond in the family and checking its appropriate development by adoption services. A key variable for children’s catch-up are adoptive parents’ socioemotional and individual features. The aim of this study is to investigate links between adoptive mothers’ individual features and behavioral problems in their children in the first year after adoption placement, by testing the moderating role of both age at adoption and maternal genetic polymorphisms. Seventy-eight adoptive mothers completed temperament and genetic measures. Mothers showed a specific pattern of interaction between basic temperament traits and genetic markers in their assessment of children’s behavioral problems; dopamine D4 receptor gene and children’s age at adoption are two moderators in the association in which mothers’ temperament was affecting the evaluation of their children’s behavioral problems. Findings highlight a still undervalued area of parenting resources in the process of post-institutionalized children’s catch-up after adoption placement, by showing how individual features count in the commonly measured variable of children’s behavioral and emotional problems. This could help in orienting identification and choice of key variables for family assessment after adoption placement, thus contributing in fostering children’s healthy development.

Behavioral addictions in early-onset Parkinson disease are associated with DRD3 variants

BackgroundImpulse control disorders (ICDs) comprise abnormal behaviors frequently found in patients with Parkinson's disease (PD) receiving antiparkinsonian medication. ICDs in PD would develop when dopaminergic treatment overstimulates the dopamine receptor D3 (DR3). Here we studied whether DR3 gene (DRD3) is associated to ICD in PD patients with early-onset (EOPD). MethodsWe performed association analysis of the rs6280 DRD3 single nucleotide variation (SNV) (Ser9Gly) in a clinical sample of 126 non early-onset PD (NEOPD) and 73 EOPD (age at onset < 45). ICD was evaluated using the Questionnaire for Impulsive-Compulsive Disorders (QUIP) in PD. ResultsIn the total sample, we found that a younger onset of PD is linked to ICD traits with a potentially addictive reinforcement (ICDARs, behavioral addictions) (p = .017) and a trend for total ICDs (p = .078) while punding was not associated (p = .75). EOPD sample showed an increase of DRD3 C+ genotype for ICD (p = .022) and ICDARs (p = .043) but not for punding (p = .170). The post-hoc analyses including the time of evolution and Pramipexol or Ropinirole treatments, confirmed the independent effect of the DRD3 upon ICDs (p = .028) and ICDARs (p = .041) as well as the interaction between DRD3 and Pramipexol treatment upon ICDARs (OR = 4.60, 95% CI 1.20–17.632, p = .026). The NEOPD group showed no association between DRD3 and ICDs. ConclusionsWe found that behavioral addictions in PD are associated with an early onset of the disease, the rs6280 DRD3 SNV and the type of dopamine agonist. Further investigation in independent samples is warranted.

Real-time assessment of alcohol craving and naltrexone treatment responsiveness in a randomized clinical trial

IntroductionThis secondary data analysis examined whether and how the dopamine receptor D4 gene (DRD4) influenced naltrexone treatment responsiveness in a randomized clinical trial. We leveraged intensive experience sampling methods to test the hypothesis that craving recorded at drinking and non-drinking moments would mediate naltrexone effects on the likelihood of heavy drinking, but only among carriers of the DRD4 long (DRD4-L) allele. MethodsParticipants (Mage=29.8years, SD=12.1) were non-treatment seeking heavy drinkers (n=104, 54.8% female, 61.5% alcohol dependent) randomized to 3weeks of daily naltrexone (50mg) or placebo. During these 3weeks, participants used handheld electronic devices to complete real-time reports of alcohol use and craving multiple times per day in their natural environments. This approach afforded intensive repeated assessment of focal variables and provided in-the-moment data to test whether craving when not drinking or early in drinking episodes explained naltrexone effects on drinking. ResultsModerated-mediation multilevel structural equation models showed that craving during non-drinking moments mediated the treatment effect of naltrexone on heavy drinking but only among carriers of the DRD4-L allele. The same pattern of associations was not shown when evaluating craving while participants were consuming alcoholic beverages. ConclusionsFindings provide the first in vivo evidence that, among carriers of the DRD4-L allele, naltrexone blunts craving in real-world settings, and this effect in turn reduces the likelihood of heavy drinking. This work highlights the utility of EMA methods for elucidating how treatments work and further demonstrates the importance of genetic factors for understanding individual differences in pharmacotherapy responsiveness.

Allele frequencies of dopamine D4 receptor gene (DRD4) and Catechol-O-methyltransferase (COMT) Val158Met polymorphism are associated with methylphenidate response in adolescents with attention deficit/hyperactivity disorder: a case control preliminary study

ABSTRACTOBJECTIVES: In this study, it was aimed to analyse the relationship between clinical improvement in adolescents with attention deficit/hyperactivity disorder (ADHD) and the presence of allele frequencies of dopamine D4 receptor (DRD4), and Val158Met polymorphism of catechol-O-methyltransferase (COMT) genes.METHODS: Thirty-four adolescents (age range, 13–18 years) with ADHD participated in this study. Thirty-two patients were males and two were females. Du Paul ADHD Rating Scale-Clinician version (ARS) and Clinical Global Impression-severity of impairment (CGI-S) were used for the evaluation of symptom severity. Fifty healthy age-matched adolescents were recruited as controls.RESULTS: When the groups with (n = 9) and without (n = 25) 7-repeat alleles for DRD4 were considered, there was a statistically significant decrease of DuPaul ARS total and hyperactivity scores in those treated with OROS-methylphenidate. When the Val/Met allele-positive group for COMT gene (n = 17) was compared with the Val/Va...

Dopamine receptor D2 genetic variations is associated with the risk and clinicopathological variables of urothelial cell carcinoma in a Taiwanese population.

Dopamine receptor D2 (DRD2) is overexpressed in several kinds of cancers and was correlated with the prognosis of these cancers. Polymorphisms within the DRD2 gene were shown to be associated with lung and colon cancers. The purpose of this study was to explore effects of DRD2 gene polymorphisms on the susceptibility to and clinicopathological characteristics of urothelial cell carcinoma (UCC). In total, 369 patients diagnosed with UCC and 738 healthy controls were enrolled to analyze DRD2 genotypes at four loci (rs1799732, -141C>del; rs1079597, TaqIB; rs6277, 957C>T; and rs1800497, TaqIA) using a TaqMan-based real-time polymerase chain reaction (PCR). We found a significantly lower risk for UCC in individuals with the DRD2 rs6277 CT genotype compared to those with the wild-type CC genotype (adjusted odds ratio (AOR)=0.405, 95% confidence interval (CI): 0.196~0.837, p=0.015). In 124 younger patients (aged < 65 years) of the recruited UCC cohort, patients who carried at least one T allele of DRD2 rs1800497 were at higher risk (AOR=2.270, 95% CI: 1.060~4.860, p=0.033) of developing an invasive stage (pT2~pT4). In 128 female patients of the recruited UCC cohort, patients who carried at least one deletion allele of DRD2 rs1799732 showed a higher incidence of having an invasive stage (AOR=2.585, 95% CI: 1.066~6.264, p=0.032) and a large tumor (AOR=2.778, 95% CI: 1.146~6.735, p=0.021). Further analyses of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed correlations of the expression of DRD2 with an invasive tumor, tumor metastasis, and the lower survival rate in patients with UCC. Our findings suggest that DRD2 levels might affect the progression of UCC, and the polymorphisms rs6277, rs1800497, and rs1799732 of DRD2 are probably associated with the susceptibility and clinicopathologic development of UCC in a Taiwanese population.

Association study between polymorphisms of dopamine transporter gene (SLC6A3), dopamine D1 receptor gene (DRD1), and autism

Introduction Autism is an etiologically and clinically heterogeneous group of disorders, collectively referred to as 'autism spectrum disorders'. Dopamine (DA) modulates a wide variety of processes, functions, and behaviors that are abnormal in individuals with autism spectrum disorders. The DA transporter gene SLC6A3 (solute carrier family 6, member 3) is a crucial regulator of DA homeostasis and neurotransmission. SLC6A3 gene has many polymorphisms which are associated with hangs in gene expression that may affect extracellular DA levels. The rs2550936 single-nucleotide polymorphism (SNP) at SLC6A3 gene decreased SLC6A3 expression or DA transporter availability. Also, the rs4532 SNP at dopamine D1 receptors (DRD1) is apparently a good candidate for affecting autism risk or modifying the classical symptoms of autism. Aim This study aimed to analyze the association between rs2550936 SNP at SLC6A3 gene and rs4532 SNP at the DRD1 gene and autism and their association with various demographical and clinical data of autistic children. Patients and methods This study included 50 autistic patients (36 males and 14 females) and 50 age-matched and sex-matched nonautistic controls for comparison. All patients were subjected to history taking, physical examination, language assessment, intelligence quotient, and childhood autism rating scale as well as analysis of SLC6A3 gene rs2550936 SNP and DRD1 gene rs4532 SNP using PCR–restriction fragment length polymorphism (RFLP), which was done for both patients and nonautistic controls. Results There has been a statistically significant relationship between the age of mother and different genotypes of SLC6A3 gene in autistic patients (P = 0.030). DRD1 rs4532 A/G and A/A genotype frequencies were significantly higher in autistic patients (52%) compared with nonautistic controls (40%) (P = 0.043). Conclusion DRD1 rs4532 polymorphism might be a risk factor increasing autism susceptibility as well as the association of the patient age with its different genotypes. There was a significant difference in the mother's age at conception and different genotypes of the SLC6A3 gene in autistic patients.

Aerobic and concentration training and allele 7 in the dopamine receptor D4 (D4DR) gene increase chances of smoking cessation in young Polish women.

IntroductionOne reason for the limited effectiveness of the available smoking cessation methods is the fact that the causes of tobacco addiction have not been adequately explained yet. Numerous anti-smoking programs aimed at women involve intense physical activity. The goal of the study was to evaluate the effectiveness of health training for smoking cessation by young women in connection with the dopamine receptor gene (D4DR) in their genetic profile.Material and methodsForty-eight adult female smokers were randomly assigned to: 1) a concentration training group, or 2) an aerobic and concentration training group. Genetic and phenotypic data were obtained from 48 participants. Genotyping was performed for allele 7 in the D4DR gene.ResultsIndividuals with allele 7 in the dopamine receptor D4 gene have two times greater chances (OR = 2.13: 95% CI: 0.91–4.96) of quitting smoking than individuals without allele 7. No statistical significance was revealed (p = 0.0805). Individuals undertaking aerobic training in combination with concentration training are three times more likely (OR = 3.06: 95% CI: 1.03–9.05) to quit smoking than individuals who do not perform aerobic training (p = 0.0439).ConclusionsThe results of the study show that an intensive, 6-week health training program had a significant influence on smoking cessation. Smoking quitters, who are genetically predisposed and decide to take up aerobic training in combination with concentration training, have much greater chances of quitting smoking.

Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction.

Heroin and methylamphetamine (METH) are two addictive drugs that cause serious problems for society. Dopamine receptor D4 (DRD4), a key receptor in the dopaminergic system, may facilitate the development of drug addiction. The aim of the present study was to investigate the association between the promoter methylation level of DRD4 gene and drug addiction. Bisulfite pyrosequencing technology was used to measure the methylation levels of DRD4 promoter in 60 drug addicts and 52 matched controls. Significantly higher levels of DRD4 CpG1 and CpG4 methylation were detected in METH and heroin drug addicts compared with controls (P<0.05). Male METH addicts exhibited significantly higher DRD4 CpG1, CpG2 and CpG4 methylation levels compared with sex-matched controls (P<0.05). In heroin addicts, a positive correlation was observed between depression-dejection and DRD4 CpG5 methylation (r=0.537, P=0.039) whereas there was a negative correlation between drug usage frequency and CpG1 methylation (r=-0.632, P=0.011). In METH addicts, methylation levels were not significantly associated with depression-dejection and drug usage frequency. In addition, luciferase assays demonstrated that the target sequence of the DRD4 promoter upregulates gene expression. The results of the present study suggest that DNA methylation of DRD4 may be responsible for the pathophysiology of drug addiction.

TAQ1A1 Allele of the DRD2 Gene Region Contribute to Shorter Survival Time in Alcohol Dependent Individuals When Controlling for the Influence of Age and Gender. A Follow-up Study of 18 Years.

To investigate the influence of the A1 allele of the TAQ1A polymorphism in the dopamine D2 receptor (DRD2) gene region on mortality in adult individuals with alcohol dependence. The study sample consisted of 359 alcohol-dependent individuals treated for severe alcohol withdrawal symptoms in 1997. Years of survival was studied in an 18-year follow-up. In the analyses, gender and age were controlled for. At the 18-year follow-up, 53% individuals had deceased. The analyses showed that older age (P < 0.001), male gender (P < 0.05) and carrying the A1 allele (P < 0.01) all significantly and independently contributed to shorten years of survival. Among the deceased individuals, the genotype A1+ was the only significant contributor to shorten years of survival. An important contribution of the present study is that in alcohol dependence the Taq1A1 allele of the DRD2 gene region is a risk factor for premature death of similar importance as the well-known risk factors of age and gender. We investigated the influence of A1 allele of the TAQ1A polymorphism in DRD2 receptor gene region on mortality in alcohol-dependent individuals in an 18-year follow-up. Age, gender and the A1 allele contributed to shorten years of survival. Among the deceased, the A1+ was the only contributor to shorten years of survival.

Potential diagnostic markers of olanzapine efficiency for acute psychosis: a focus on peripheral biogenic amines

BackgroundBiomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients.MethodsThis research included 60 patients with acute psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment.ResultsThe administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes.A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group.ConclusionsThe DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.

Preliminary Evidence for an Association Between Variants of the Catechol-O-Methyltransferase (COMT) Gene and Premature Ejaculation

BackgroundStudies have suggested that dopamine plays a role in the neurobiological mechanism that triggers ejaculation, leading scientists to hypothesize that dopamine-related genetic polymorphisms could contribute to symptoms of premature ejaculation (PE). AimTo investigate associations between dopamine receptor and catechol-O-methyltransferase (COMT; an enzyme involved in the catabolism of dopamine) gene-linked polymorphisms and PE. MethodsPE status in patient groups was determined by clinical diagnosis performed by a physician specializing in sexual medicine. Self-reported PE symptoms from a validated questionnaire also were reported. Saliva samples were collected from 149 patients with PE and 1,022 controls from a population-based sample. In total, we tested associations between PE and 11 single-nucleotide polymorphisms in the dopamine receptor D1, D2, and D3 genes and in the COMT gene. OutcomesWe found no associations between dopamine receptor gene polymorphisms and PE, but 2 COMT-linked loci (rs4680 and rs4818) had significant associations after correction for multiple testing. Results1 COMT gene-linked locus that was associated with PE symptoms in the present study, rs4680, is a well-documented functional polymorphism that causes a valine-to-methionine substitution. The other polymorphism, rs4818, is in high linkage disequilibrium with the rs4680 locus, indicating that they capture the same effect. Surprisingly, the rs4680 variant that was statistically significantly more prevalent in the PE group (ie, the valine-encoding allele) has been associated with higher enzymatic activity and therefore lower synaptic dopamine levels. Clinical TranslationDrugs targeting the dopaminergic system could affect PE symptoms. Strengths and LimitationsNo replication sample was available for the present study; thus, our findings should be interpreted with caution. Moreover, a limitation of our study is the small sample in the context of genetic association studies (although it should be mentioned that genetically informative samples with phenotypic information about PE symptoms are scarce, and most previous genetic association studies of PE have used samples of similar or smaller size). However, our results are plausible: we report an association between one of the most extensively studied and understood genetic polymorphisms in psychiatric research and PE, and our results are in line with the long-standing hypothesis that dopamine influences human ejaculatory function. ConclusionsWe report an association between 2 COMT gene-linked loci and PE symptoms, but our results should be treated with caution until independently replicated.Jern P, Johansson A, Strohmaier J, et al. Preliminary Evidence for an Association Between Variants of the Catechol-O-Methyltransferase (COMT) Gene and Premature Ejaculation. J Sex Med 2017;14:1558–1565.

The dopamine D4 receptor gene, birth weight, maternal depression, maternal attention, and the prediction of disorganized attachment at 36 months of age: A prospective gene × environment analysis

BackgroundEfforts to understand the developmental pathways for disorganized attachment reflect the importance of disorganized attachment on the prediction of future psychopathology. The inconsistent findings on the prediction of disorganized attachment from the dopamine D4 receptor (DRD4) gene, birth weight, and maternal depression as well as the evidence supporting the contribution of early maternal care, suggest the importance of exploring a gene by environment model. MethodsOur sample is from the Maternal Adversity, Vulnerability, and Neurodevelopment project; consisting of 655 mother–child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 genotype was obtained with buccal swabs and categorized according to the presence of the 7-repeat allele. Maternal depression was assessed with the Center for Epidemiologic Studies Depression Scale at the prenatal, 6-, 12-, and 24-month assessments. Maternal attention was measured at 6-months using a videotaped session of a 20-min non-feeding interaction. Attachment was assessed at 36-months using the Strange Situation Procedure. ResultsThe presence of the DRD4 7-repeat allele was associated with less disorganized attachment, β=−1.11, OR=0.33, p=0.0008. Maternal looking away frequency showed significant interactions with maternal depression at the prenatal assessment, β=0.003, OR=1.003, p=0.023, and at 24 months, β=0.004, OR=1.004, p=0.021, as at both time points, women suffering from depression and with frequent looking away behavior had an increased probability of disorganized attachment in their child, while those with less looking away behavior had a decreased probability of disorganized attachment in their child at 36 months. ConclusionsOur models support the contribution of biological and multiple environmental factors in the complex prediction of disorganized attachment at 36 months.

The interaction of DRD2 and parenting style in predicting creativity

The present study examined the interaction of dopamine D2 receptor gene (DRD2) and parenting style on creativity. Participants were 427 Chinese undergraduate students from a project designed to identify the genetic basis of creativity. The result showed that there was significant interaction between DRD2 and authoritarian parenting when predicting creativity. Specifically, it was found that the negative effect of mother/father authoritarianism on creativity was only present when individuals were carriers of DRD2 Del (rs1799732) allele. No significant interaction of DRD2 and authoritative or permissive parenting was found. In conclusion, the present study provides the first preliminary evidence for the effect of DRD2-parenting interaction on creativity; future studies are warranted to validate these findings.

Evaluation of the Abuse Potential of Novel Amphetamine Derivatives with Modifications on the Amine (NBNA) and Phenyl (EDA, PMEA, 2-APN) Sites.

Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.

No association between dopamine D3 receptor gene Ser9Gly polymorphism (rs6280) and risk of schizophrenia: an updated meta-analysis.

ObjectiveSer9Gly (rs6280) is a functional single-nucleotide polymorphism (SNP) in the dopamine receptor D3 (DRD3) gene that may be associated with schizophrenia. We performed a meta-analysis to determine whether Ser9Gly influences the risk of schizophrenia and examined the relationship between the Ser9Gly SNP and the etiology of schizophrenia.MethodsCase–control studies were retrieved from literature databases in accordance with established inclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between Ser9Gly and schizophrenia. Subgroup analysis and sensitivity analysis were also performed.ResultsSeventy-three studies comprising 10,634 patients with schizophrenia (cases) and 11,258 controls were included in this meta-analysis. Summary results indicated no association between Ser9Gly and risk of schizophrenia. In the dominant genetic model, the pooled OR using a random effects model was 0.950 (95% CI, 0.847–1.064; P=0.374).ConclusionResults of this meta-analysis suggest that the Ser9Gly SNP is not associated with schizophrenia. These data provide possible avenues for future case–control studies related to schizophrenia.

The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children

ObjectiveThe aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. MethodsThis case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified. ResultsChildren with ADHD had significantly higher dimethylphosphate (DMP, 236.69nmol/g cre. vs. 186.84nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95µg/g cre. vs. 16.55µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24–0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13–1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12–65.04). ConclusionThis study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected.

Selection on a behaviour-related gene during the first stages of the biological invasion pathway.

Human-induced biological invasions are common worldwide and often have negative impacts on wildlife and human societies. Several studies have shown evidence for selection on invaders after introduction to the new range. However, selective processes already acting prior to introduction have been largely neglected. Here, we tested whether such early selection acts on known behaviour-related gene variants in the yellow-crowned bishop (Euplectes afer), a pet-traded African songbird. We tested for nonrandom allele frequency changes after trapping, acclimation and survival in captivity. We also compared the native source population with two independent invasive populations. Allele frequencies of two SNPs in the dopamine receptor D4 (DRD4) gene-known to be linked to behavioural activity in response to novelty in this species-significantly changed over all early invasion stages. They also differed between the African native population and the two invading European populations. The two-locus genotype associated with reduced activity declined consistently, but strongest at the trapping stage. Overall genetic diversity did not substantially decrease, and there is little evidence for new alleles in the introduced populations, indicating that selection at the DRD4 gene predominantly worked on the standing genetic variation already present in the native population. Our study demonstrates selection on a behaviour-related gene during the first stages of a biological invasion. Thus, pre-establishment stages of a biological invasion do not only determine the number of propagules that are introduced (their quantity), but also their phenotypic and genetic characteristics (their quality).

P.3.d.046 - Effect of dopamine D2 receptor and serotonin 2A receptor gene polymorphisms on response to risperidone in schizophrenia

P.3.d.046 - Effect of dopamine D2 receptor and serotonin 2A receptor gene polymorphisms on response to risperidone in schizophrenia