Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or alcohol dependence through reward circuitry. This study aimed at further understanding 17β-estradiol and dopamine D2 receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female rats weighing 200 - 205 g, individually-housed, were divided into non-ovariectomized control (C = 6 groups) and ovariectomized rats (OVX = 6 groups) which were concurrently subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 μg/kg, s.c.), sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6 constitutive groups of either control or ovariectomy. Within each experimental group, consumption of different solutions (10% alcohol, 10% sucrose and water) as well as food intake and body weight were daily measured, for 10 consecutive days. Results: This study indicated that D2S was a specific inducer of alcohol and food intakes, but reduced sugar consumption. In addition, 17β- estradiol regulated the body weight set point, modulating D2S functions towards increased food intake at lower weights and decreased food intake at higher weights. D2S met the slow genomic actions induced by 17β-estradiol. Conversely, D2L inhibited alcohol and food intakes, but induced specifically sugar consumption, thereby regulating blood glucose levels and promoting energy expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by OVX, exacerbating sugar intake and increasing body weight. D2L mediated the rapid metabolic effects of 17β-estradiol. Conclusion: Our results supported physiological data reporting that activation of the mostly expressed presynaptically D2S-class autoreceptors decreased dopamine release stimulating food intake, whereas activation of the predominantly postsynaptic isoform D2L receptors increased dopamine activity inhibiting food intake. Our studies indicated that 17β-estradiol acted on the two types of D2 receptors showing opposite functions to equilibrate energy intake vs. expenditure for weight set point regulation. Our data also supported biochemical findings reporting that 17β-estradiol induced D2 genes transcriptional regulation, thereby involving both types of D2 receptors in the etiology of obesity. The combined dysregulated effects of D2L and D2S receptors, as 17β-estradiol was lacking, would be causal factors underlying the etiology of obesity.

Relationship between electroacupuncture analgesia and dopamine receptors in nucleus accumbens

目的：研究多巴胺受体拮抗剂左旋四氢巴马汀（ｌＴＨＰ）加强电针镇痛（ＥＡＡ）的原理，阐明中枢神经系统内多巴胺（ＤＡ）系统在ＥＡＡ中的作用．方法：分别将Ｄ１受体激动剂ＳＫ＆Ｆ３８３９３和Ｄ２受体激动剂ｑｕｉｎｐｉｒｏｌｅｈｙｄｒｏｃｈｌｏｒｉｄｅ（Ｑｕｉ）注射入大鼠伏膈核，观察对ＥＡＡ及ｌＴＨＰ加强ＥＡＡ的作用．结果：ＳＫ＆Ｆ３８３９３（５μｇ，１０μｇ）明显对抗了ｌＴＨＰ加强ＥＡＡ的作用，１０μｇＳＫ＆Ｆ３８３９３则减弱ＥＡＡ；Ｑｕｉ（１０μｇ，２０μｇ），对ＥＡＡ及ｌＴＨＰ加强ＥＡＡ的作用没有显著影响．结论：伏膈核内Ｄ１受体活动在ＥＡＡ及ｌＴＨＰ加强ＥＡＡ中起重要作用，Ｄ２受体没有显著作用．

Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain

Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,which are the predominant neurons in the LEC that project to the DG,remain elusive.Here,we investigated possible mechanisms using a rat model of complete Freund’s adjuvant(CFA)-induced inflammatory pain.We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents(Ih),which led to the hyperexcitability of LEC fan cells of CFA slices.This phenomenon was attenuated in CFA slices by activating dopamine D2,but not D1,receptors.Chemogenetic activation of the ventral tegmental area-LEC projection had a D2 receptor-dependent analgesic effect.Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity,and this effect was attenuated by pre-activation of the Ih.Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.

Effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization in high myopia mice

AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,and the high myopia was diagnosed by optometry,the diopter was less than-6.00 D,and CNV was induced by 532 nm laser.The changes of dopamine D1 receptor(DRD1),dopamine D2 receptor(DRD2),and vascular endothelial growth factor A(VEGFA)were detected by Western blot technology at 0.5,1,2h,and 7d after 0.01%,0.05%,and 0.1%atropine eye drops,respectively,the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group,and the higher the concentration,the more significant the inhibitory effect(P<0.05).CONCLUSION:The 0.01%,0.05%,0.1%atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1,and the effect of 0.05%and 0.1%atropine eye drops is more significant.

Modeling of Dopamine D2 Receptor and its Agonist DOCK Analyses

A model of transmembrane helices of dopamine D2 receptor was constructed using the X ray coordinates of bacteriorhodopsin (BR) as a template. Based on the results from the model and the site directed mutagenesis experience, the binding pocket, including nine amino acid residues beside indispensable Asp86, Ser141 and Ser144 residues, was defined. In order to testify the 3D structure of dopamine D2 receptor and specially test the binding sites, two sets of D2 receptor agonists (one was rigid and the other flexible) were selected for docking. A good result of correlation between logIC 50 and binding energy E b indicates that the predicted model is reliable for the investigation of the receptor ligand interaction and design of new active molecules.

Down-regulation of dopamine D2 receptor associates with impaired reversal learning induced by morphine withdrawal

OBJECTIVE Cognitive inflexibility plays a critical role in the compulsive drug taking,a central characteristic of drug addictions,yet its underlying neurochemical mechanisms are not well understood.The present study examined the impact of morphine withdrawal on reversal learning.METHODS Reversal learning was tested in a four-choices digging task.Some brain tissues were harvested 2 h after the behavioral experiment for the further measurement.RESULTS We found that after long-term abstinence for a month from chronic morphine exposure,mice exhibited a profound reversal learning deficit.We further found that dopamine D2 receptor(D2R)system in the frontal-striatal circuit is significantly down-regulated,at both receptor and downstream signals levels.Subsequent pharmacological experiments demonstrated that aripiprazole,a D2R partial agonist,prevented the D2R downregulation and rescued the reversal learning deficit.CONCLUSION Together,our findings provide valuable insights into the causal relationship between D2R system in the frontal-striatal circuit and the cognitive inflexibility caused by abused drugs and offer a promising possibility of an effective therapeutic intervention for drug addictions.

Effects of septal nucleus lesion on dopamine D_2 receptor expression in the prefrontal lobe, striatum, and brainstem in a rat model of schizophrenia

BACKGROUND： It has been demonstrated that the septal nucleus is involved in the pathogenesis of schizophrenia. Based on autopsies of schizophrenia patients, studies have shown a reduced number of septal nucleus neurons and glia. In addition, experimental rat models of schizophrenia have shown increased dopamine receptor D2 binding sites in the basal ganglia, septal nuclei, and substantia nigra. Previous studies have demonstrated that the septal nucleus modulates dopamine metabolic disorder and dopamine D2 receptor balance. OBJECTIVE： Dopamine D2 receptor expression in a rat model of schizophrenia, combined with antipsychotic drugs, was analyzed in the prefrontal lobe, striatum, and brainstem. In situ hybridization was used to observe the effects of stereotactic septal nucleus lesions on dopamine D2 receptor expression in the brains of methylamphetamine-treated rats. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed in the Laboratory of General Institute of Psychosurgery, Third Hospital of Chinese PLA from November 2005 to June 2006. MATERIALS： A total of 120 healthy, adult Sprague Dawley rats, weighing approximately 200 g, were included. Methylamphetamine （Sigma, USA） and an in situ hybridization detection kit for dopamine D2 receptor （Boster, China） were also used for this study. METHODS： All rats were randomly allocated to the following 4 groups, with 30 rats in each group： normal control, simple administration, septal nucleus lesion, and sham-operated groups. In the normal control group, rats were not administered or lesioned. In the remaining 3 groups, rats were intraperitoneally administered 10 mg/kg methylamphetamine, once per day, for 15 successive days to establish a schizophrenia model. Following successful model establishment, rats from the septal nucleus lesion group were subjected to stereotactic septal nucleus lesions. The cranial bone was exposed in rats from the sham-operated group, and the septal nucleus was not lesioned. MAIN OUTCOME MEASURES： At 7 days post-surgery, dopamine D2 receptor expression in the prefrontal lobe, striatum, and brainstem were detected by in situ hybridization. RESULTS： Dopamine D2 receptor expression in the rat prefrontal lobe, striatum, and brainstem was significantly higher in the simple administration group and sham-operated group, compared with the normal control group （P 〈 0.01）. In the septal nucleus lesion group, dopamine D2 receptor expression was significantly less than the simple administration and sham-operated groups, （P 〈 0.01）. There was no significant difference in dopamine D2 receptor expression between the simple administration and sham-operated groups （P 〉 0.05）. CONCLUSION： Septal nucleus lesions reduce dopamine D2 receptor expression in the prefrontal lobe, striatum, and brainstem in a rat model of schizophrenia, indicating that the septal nucleus modulates dopamine D2 receptor expression.

Effect of total isoflavones from pueraria lobata on the expressions of preproenkephalin, prodynorphin and D2 dopamine receptor mRNA in PC12 cells induced by MPP^+

Objective： The aim of the study was to observe the effect of total isoflavones from pueraria Iobata （TIP） on D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions in Parkinson＇s disease （PD） model cells induced by 1-methyl-4-phenylpyridinium ion （MPP^＋）. Methods： TIP was dissolved in 0.1 M NaOH and added to the culture medium at a final concentrations of 50 mg/L, 100 mg/L and 200 mg/L. Some cells （control） were exposed to 0.001 M NaOH. TIP was added to PC12 cells 30 min prior to the administration of MPP^＋. TIP and MPP^＋ remained in the culture medium for 96 h. D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions were assayed by real-time quantitative reverse transcription-PCR. Results： The D2 dopamine receptor mRNA and preproenkephalin mRNA expressions were up-regulated in MPP^＋ group compared with the control group, and prodynorphin mRNA expression was down-regulated in that. The D2 dopamine receptor mRNA expression being down-regulated and prodynorphin mRNA expression being up-regulated in TIP group compared with the MPP^＋ group. And there was no effect of TIP on preproenkephalin gene expression in PC12 cells induced by MPP^＋. Conclusion： The results suggest that TIP down-regulates the D2 dopamine receptor mRNA expression, up-regulates prodynorphin mRNA expression and not affects preproenkephalin gene expression in PC12 cells induced by MPP^＋.

The hypothalamic-spinal dopaminergic system:a target for pain modulation

Nociceptive signals conveyed to the dorsal horn of the spinal cord by primary nociceptors are subject to extensive modulation by local neurons and by supraspinal descending pathways to the spinal cord before being relayed to higher brain centers. Descending modulatory pathways to the spinal cord comprise,among others, noradrenergic, serotonergic, γ-aminobutyric acid(GABA)ergic, and dopaminergic fibers.The contributions of noradrenaline, serotonin, and GABA to pain modulation have been extensively investigated. In contrast, the contributions of dopamine to pain modulation remain poorly understood.The focus of this review is to summarize the current knowledge of the contributions of dopamine to pain modulation. Hypothalamic A11 dopaminergic neurons project to all levels of the spinal cord and provide the main source of spinal dopamine. Dopamine receptors are expressed in primary nociceptors as well as in spinal neurons located in different laminae in the dorsal horn of the spinal cord, suggesting that dopamine can modulate pain signals by acting at both presynaptic and postsynaptic targets. Here, I will review the literature on the effects of dopamine and dopamine receptor agonists/antagonists on the excitability of primary nociceptors, the effects of dopamine on the synaptic transmission between primary nociceptors and dorsal horn neurons, and the effects of dopamine on pain in rodents. Published data support both anti-nociceptive effects of dopamine mediated by D2-like receptors and pro-nociceptive effects mediated by D1-like receptors.

SOX2/DRD2 signaling pathway facilitates astrocytic dedifferentiation in cerebral ischemic mice

Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cerebral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expression of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluorescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedifferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,significantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydrocholoride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedifferentiation and may be used to treat ischemic stroke.

Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia

Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups （n = 8 in each group）： Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. Cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine 92 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury.

Renaldopaminergic system:Pathophysiological implications andclinical perspectives

Fluid homeostasis, blood pressure and redox balance in the kidney are regulated by an intricate interaction between local and systemic anti-natriuretic and natriuretic systems. Intrarenal dopamine plays a central role on this interactive network. By activating specifc receptors, dopamine promotes sodium excretion and stimulates anti-oxidant and anti-inflammatory pathways. Different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome, hypertension and renal infammation, can be associated with impaired action of renal dopamine including alteration in biosynthesis, dopamine receptor expression and signal transduction. Given its properties on the regulation of renal blood fow and sodium excretion, exogenous dopamine has been postulated as a potential therapeutic strategy to preventrenal failure in critically ill patients. The aim of this review is to update and discuss on the most recent findings about renal dopaminergic system and its role in several diseases involving the kidneys and the potential use of dopamine as a nephroprotective agent.

Variation in the <i>DRD2</i>gene affects impulsivity in intertemporal choice

Introduction: Impulsivity in intertemporal choice has been operationalized as “delay discounting,” referring to the preference for a sooner, smaller reward in neuroeconomics. It is reportedly associated with the dopaminergic systems. Dopamine receptor D2 (DRD2) is the D2 subtype of the dopamine receptor of the G-protein coupled receptor family. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) in DRD2 gene on delay discounting. Methods: The participants consisted of 91 healthy Japanese people (66 males and 25 females with a mean age of 40.9 ± 6.9 years). Each participant completed the Kirby’s monetary choice questionnaire (MCQ) for delayed gain and donated a whole blood sample. Two SNPs (C957T (rs6277) and TaqI A (rs1800497)) in DRD2 were genotyped by using the DigiTag2 assay. SNP linear regression analyses with 100,000 permutations were conducted for the hyperbolic time-discount rate (k). Results: The SNP C957T showed a significant association;participants with more minor alleles (T) were more impulsive in intertemporal choice for delayed gain (multiplicity-corrected P = 0.041 with a small effect size). Conclusion: The variation in the DRD2 gene is associated with impulsive decision-making. This is the first study to demonstrate an association between DRD2 and impulsivity in intertemporal choice with a multiplicity-corrected significance.

多巴胺D_2受体TaqIA多态性与海洛因依赖行为相关性

目的 :探讨多巴胺 (DA)受体D2 亚型基因TaqIA多态性与海洛因依赖者行为之间的相关性。方法 :应用PCR -RFLP法对 6 6例海洛因依赖病人与 132例正常人D2 R基因的TaqIA多态性特征进行对照研究。以A型行为问卷 (TABPQ) [1] 测评海洛因依赖者的行为类型 ,与其TaqIA多态性特征进行相关分析。结果 :海洛因依赖组与正常对照组DRD2 基因的TaqIA多态性基因型及等位基因频率有显著性差异 (前者携带A1等位基因的频率为 0 6 1,后者携带A1等位基因的频率为 0 31,P <0 0 5 ) ,携带A1等位基因更易形成海洛因依赖者 (比值比OR :3 47,P <0 0 5 )。各种行为类型的海洛因依赖者之间 ,基因型 (TaqIA多态性 )无显著性差异 (P >0 0 5 )。结论 :多巴胺D2 受体基因的TaqIA多态性与海洛因依赖相关连。多巴胺D2 受体基因TaqIA多态性与海洛因依赖者成瘾性的形成可能相关。这种基因位点特征可能与其他候选基因及环境因素共同作用 。

吗啡依赖大鼠脑多巴胺转运蛋白及D_2受体的研究

目的 观察吗啡依赖 (MD)大鼠脑多巴胺 (DA)系统的变化。方法 采用两隔室 (C1及C2 )模型训练大鼠对吗啡产生条件性位置偏爱 ,造成MD大鼠模型 ,用DA转运蛋白 (DAT)及DAD2 受体显像剂12 5I 甲苯 3β (4 碘苯基 )托烷 2 β 羟酸酯 (β CIT)、12 5I 左旋 3 碘 2 羟基 6 甲氧基 N[(1 乙基 2 吡咯烷 )甲基 ]苯酰胺 (IBZM)脑放射自显影、脑内放射性分布观察MD及对照组大鼠脑内D2 受体及DAT的变化。结果 条件性位置偏爱实验自第 6d后MD组大鼠由C1进入C2时间平均 (0 84±0 5 0 )min ,与对照组 (2 .40± 1.10 )min比较差异有显著性 (P <0 .0 5 ) ;放射自显影图像分析示 :12 5I β CITMD组纹状体 (ST) /小脑 (CB)及伏隔核 (NAC) /CB摄取比值分别为 4.76± 0 .92、2 .72± 0 96 ,与对照组 (5 .92± 0 .6 7、4.16± 0 .5 6 )比较差异有显著性 (P <0 .0 5 ) ;12 5I IBZM在MD组的ST/CB和NAC/CB摄取比值分别为 4.11± 0 .5 6、2 .6 4± 0 .2 5 ,明显低于对照组 (5 .43± 0 .74、3.49± 0 .6 5 ,P <0 0 5 ) ,脑内分布研究 (%ID/g脑组织湿重 )也证实MD组12 5I β CIT、12 5I IBZMST/CB摄取比值分别比对照组降低(2 1 6 8± 11.11) %和 (18.6 9± 9.97) %。结论 应用12 5I β CIT、12 5I IBZM能够敏感地反映MD?

多巴胺D_2受体显像剂Epidepride的合成及其^(131)I标记

以 3-甲氧基水杨酸为原料合成了 Epidepride[S- ( - ) - N- [( 1-乙基 - 2 -吡咯烷基 )甲基 ]- 5-碘 - 2 ,3-二甲氧基苯甲酰胺 ]及其标记前体 ( S- ( - ) - 5- (三正丁基锡 ) - N- [( 1-乙基 - 2 -吡咯烷基 )甲基 ]2 ,3-二甲氧基苯甲酰胺 ) ,并采用双氧水法对标记前体进行 131I标记 ,获得 131I- epidepride,标记率和放化纯度均大于 95%。13 1I- epidepride溶液体外稳定性好 ,4℃放置 15d放化纯度仍大于 90 %。131I- epide-pride与 D2 受体亲和力高 ,大鼠脑内纹状体与小脑的摄取比在 32 0 min时高达 2 37;在脑内纹状体的吸收可被 Spiperone完全阻断。因此 ,131I- epidepride有望成为多巴胺 D2 受体 SPECT显像剂。

海洛因成瘾易感性与腹侧被盖区多巴胺D2受体及多巴胺转运体的关系

目的建立大鼠海洛因成瘾易感性差异模型,探讨其可能的腹侧被盖区(VTA)D2受体(D2R)及多巴胺转运体(DAT)机制。方法 130只雄性SD大鼠随机分为海洛因成瘾组(n=100)和对照组(n=30)接受7d的条件性位置偏爱(CPP)训练和2d的测评,期间两组分别给予海洛因和生理盐水注射处理。此后,成瘾组根据海洛因诱导的CPP强度挑选出高CPP组(n=30)和低CPP组(n=30)。各组大鼠再随机分为5组,在接受末次处理后分别于成瘾期、戒断第1、3、7、14天检测VTA区D2R和DAT的蛋白表达,蛋白检测采用免疫组织化学法。结果与对照组相比,高CPP组和低CPP组大鼠在成瘾期VTA区D2R和DAT蛋白表达均下降(P<0.05);戒断后第1、3、7、14天D2R及戒断第1、3天DAT仍低于对照组(P<0.05),而戒断第7、14天高、低CPP组分别与对照组的DAT差异均已无统计学意义(P<0.05);在所有检测时点,高CPP组VTA区D2R下调均比低CPP组大鼠更为明显(P<0.05),而两组的DAT表达差异均无统计学意义(P>0.05)。结论海洛因慢性处理可诱导大鼠VTA区D2R和DAT下调;而海洛因成瘾易感性可能与VTA区低D2R有关,但未见与DAT相关。

端粒酶永生化的人单克隆神经前体细胞系诱导表达多巴胺D_2受体

目的 :检测人神经前体细胞系HNG12 10 E能否诱导表达多巴胺D2 受体mRNA和受体蛋白 ,表达的受体是否有生理功能。方法 :细胞因子诱导分化 ,RT PCR和免疫荧光染色检测D2 的表达 ;Fluo 3测定多巴胺刺激产生的胞浆Ca2 + 。结果 :RT PCR显示D2 mRNA诱导后阳性 ,免疫荧光结果显示诱导后D2 受体蛋白在细胞膜表面阳性 ,Fluo3法测定胞浆Ca2 + ,结果显示诱导后的细胞对 5mmol·L-1多巴胺递质反应使胞浆Ca2 + 快速上升。结论 :从mRNA、蛋白和生理功能 3个层次均证明HNG12 10 E细胞系诱导后表达D2 。

不同证候的注意缺陷多动障碍患儿多巴胺D_2受体基因携带情况检测

注意缺陷多动障碍（ａｔｅｎｔｉｏｎｄｅｆｉｃｉｔｈｙｐｅｒｃａｔｉｖｉｔｙｄｉｓｏｒｄｅｒ，ＡＤＨＤ）是常见的儿童行为障碍，目前病因尚未明确。国外近年由于分子生物学方法的介入，发现多巴胺Ｄ２受体ＴａｑＩＡ１等位基因与本病相关。通过对广州市城镇学龄儿童多巴胺Ｄ２受体基因ＴａｑＩＡ多态性的检测，支持Ａ１等位基因与本病的关系（Ｐ＝０．００６５２０）；并发现该基因与中医辨证的“肾虚肝亢”证候关系更为密切（Ｐ＝０．０００１２２），而“心脾不足”证候则与正常对照组间无显著性差异（Ｐ＝０．９１０９５２），因而在基因水平上为ＡＤＨＤ的中医辨证提供了参考思路。

多巴胺D_2受体基因启动子A-241G多态性在精神分裂症家系中的连锁不平衡传递

目的 :探讨多巴胺D2 受体基因 (dopamineD2 receptor,DRD2 )启动子A 2 41G多态性与精神分裂症的关系。方法 :采集 10 1个家系 ,每家有 2名或 2名以上符合ICD 10精神分裂症诊断标准患病同胞且父母存活。对DRD2启动子的A 2 41G多态性进行检测。结果 :(1)DRD2启动子的A 2 41G等位基因频度和基因型频度在父母组、非患病同胞组和患病同胞组之间差异无显著性 ,在 3组不同性别之间以及在精神分裂症不同亚型之间基因型频度和等位基因频度的分布差异亦无显著性 ;(2 )传递不平衡检验发现在患病同胞 (χ2 =0 .94,P >0 .0 5 ,OR =0 .83,95 %可信区间 0 .5 7～ 1.2 1)中未表现传递不平衡性 ,而在非患病同胞 (χ2 =6 .76 ,P <0 .0 1,OR =3 .17,95 %可信区间 0 .41～ 2 4.71)中存在传递不平衡性 ,其中 2 41A等位基因在非患病同胞中传递较多 ;(3)基因型与妄想总分、幻觉总分、思维形式障碍、情感障碍、精神性失语及症状持续时间等临床特征相关。结论 :DRD2启动子的A 2