Dopamine D1 receptor in ventrolateral periaqueductal gray modulates propofol anesthesia in rats / 医学研究生学报

ObjectiveVentrolateral periaqueductal gray (vlPAG) locates in ascending reticular activating system, which plays a key role in the sleep-wake circle. However, the role of vlPAG in general anesthesia has not been identified. To investigate the effect of the dopamine receptor in vlPAG neurons on propofol anesthesia, we used real-time in vivo fiber photometry, microinjection and EEG.MethodsTo observe the alteration of neuronal activity in the vlPAG throughout propofol anesthesia, 10 Sprague-Dawley rats were used for calcium fiber photometry recording. 50 vlPAG bilateral microinjection models were established and assigned into five groups randomly, including D1R agonist group, D1R antagonist group, D2R agonist group, D2R antagonist group, and control group (n=10). Under propofol anesthesia, 1 μL of D1R agonist, D1R antagonist, D2R agonist, D2R antagonist, and isotonic saline were microinjected into the vlPAG of animals in the corresponding groups, respectively. The induction time, recovery time and the changes in electroencephalogram (EEG) before and after microinjection were recorded and analyzed.ResultsThe neuronal activity in the vlPAG was significantly inhibited during the induction period and markedly recovered during the recovery period from propofol anesthesia (P<0.05). Subsequently, the microinjection of D1R agonist into the vlPAG notably prolonged the induction time and reduced the emergence time of propofol anesthesia with a decrease of δ-band ratio. While the microinjection of D1R antagonist accelerated the induction time and prolonged the emergence time of propofol anesthesia with an increase of δ-band ratio and a decrease in β-band ratio in cortical EEG (P<0.05). The induction and recovery time of D2R agonist /antagonist group did not differ with those of control group. As well, EEG before and after microinjection in D2R agonist /antagonist group did not different.ConclusionThese results indicate that vlPAG modulates the process of propofol anesthesia via D1R.

Comparison of dopamine D2 receptor (homology model and X-ray structure) and virtual screening protocol validation for the antagonism mechanism

The present research work aims to compare the homology model and recent X-ray crystal structure of dopamineD2 receptor (PDB Code: 6CM4) as well as to validate the virtual screening protocol for antagonist compounds. Thecomparison involved the sequence similarity and the capability of both proteins to produce similar risperidone bindingpose with co-crystal structure based on ChemPLP score and Tanimoto Coefficient score generated by PLANTS andPyplif. Homology model failed to give the correct binding pose as the root mean square deviation fell to >2Å evenwith similar sequence and folding. Therefore, 6CM4 should be used for virtual screening instead of the homologymodel. The virtual screening protocol validation of 6CM4 was performed by PLANTS followed by Pyplif filtering.The protocol was able to give EF1% value of 6.238, which was better than the EF1% value of protein dopamine D3receptor that shared >80% similarity with dopamine D2 receptor. Similarity between the docking pose and the actualpose is considered important to obtain better predictivity

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.

Effect of Electroacupuncture at "Neiguan" (PC 6) and "Tianshu" (ST 25) for Colonic Motility and D 2 Receptor in Irritable Bowel Syndrome Rats / 针刺研究

OBJECTIVE: To observe and compare the effects of electroacupuncture (EA) at "Tianshu" (ST 25) and "Neiguan" (PC 6) for colonic motility and the expression of colon dopamine D 2 in irritable bowel syndrome (IBS) rats, and to explore the specificity of different meridians and different acupoints. METHODS: Forty Wistar newborn rats were randomly divided into blank, model, Tianshu and Neiguan groups. Separation of mother and child and acetic acid coloclyster combined with colorectal distension were used to establish IBS model in the model, Tianshu and Neiguan groups. At the age of 9 weeks, EA at bilateral ST 25 and PC 6 were applied in the corresponding groups 5 times, once every other day. After the intervention, the Bristol fecal score, the latent period of abdominal retraction reflex and the number of contraction waves were recorded. The expression of dopamine D 2 receptor was detected by immunohistochemistry. RESULTS: Compared with the blank group, the Bristol fecal score of the model group was higher (P<0.01), the 1st contraction wave latent period was shorter (P<0.01), the number of contraction waves in 90 s increased (P<0.01), the immunoreactive expression of D 2 receptor in colon decreased (P<0.01). Compared with the model group, the Bristol fecal scores of the Tianshu and Neiguan groups decreased (P<0.01), the 1st contraction wave latent periods were longer (P<0.01), the numbers of contraction waves in 90 s decreased (P<0.01), the positive expressions of D 2 receptor in colon increased (P<0.01, P<0.05). Compared with the Tianshu group, the immunoreactive expression of D 2 receptor in the Neiguan group decreased (P<0.01). CONCLUSION: EA at ST 25 and PC 6 can improve the symptoms of colonic motility in IBS rats. The effect of EA at ST 25 is better, which indicates that different meridians and different acupoints play specific effects.

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.

Multiple modalities PET/CT neuroimaging for the diagnosis of Parkinson's disease and multiple system atrophy: statistical parametric mapping analysis / 中华神经科杂志

Objective To investigate the topographic distributions of dopamine transporter (DAT),dopamine D2 receptor and glucose in Parkinson's disease (PD) and multiple system atrophy (MSA) using positron emission tomography/computed tomography (PET/CT) scanning and statistical parametric mapping (SPM) analysis.Methods Seventy subjects (39 PD patients,15 MSA patients and 16 normal controls) who came from People's Liberation Army General Hospital from September 2013 to November 2015 underwent DAT,D2 receptor and glucose brain PET/CT scans using 11 C-methyl-N-2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane (11C-β-CFT),11C-raclopride and 18F-fluorodeoxyglucose (18 F-FDG) as radiotracers,respectively.The uptake patterns were analyzed using SPM software.Results Striatal DAT binding decreased in the putamen in PD patients compared with controls (Z =5.21-5.77,P =0.002-0.016).D2 receptor showed no significant differences.However,glucose uptake decreased in cingulate gyrus(Z =4.51-4.67,P =0.010-0.017).For MSA patients,both DAT and D2 receptor binding decreased in the putamen(Z =2.13-3.42,P =0.000-0.016).Glucose uptake decreased in the bilateral putamen,cerebellum and part of frontal temporal lobes (Z =1.86-3.75,P =0.000-0.032).Conclusion Multiple modalities PET/CT scans using the ligands 11 C-β-CFT,11C-raclopride,and 18F-FDG are valuable in diagnosis of MSA and differential diagnosis of MSA from PD.

Frequência de polimorfismos genéticos rs1800497, rs1799732, rs6280 e a ocorrência da esquizofrenia refratária / Frecuencia de polimorfismos genéticos rs1800497, rs1799732, rs6280 y la ocurrencia de la esquizofrenia refractory / Frequency of genetic polymorphisms rs1800497, rs1799732, rs6280 and the occurrence of schizophrenia refractory

Introdução: a esquizofrenia é considerada um dos mais severos e complexos transtornos mentais que acomete tanto a qualidade de vida do indivíduo que convive com a doença quanto a de sua família. Caracteriza-se principalmente por sintomas denominados positivos (alteração no processo do pensamento, percepções e afeto) e negativos (embotamento afetivo-volitivo,perdas cognitivas e sintomas depressivos). Os fatores de risco para este transtorno são epifenômenos de processos fisiopatológicos que resultam de uma interação gene-ambiente ainda pouco compreendida. A hipótese da dopamina é o principal conceito que fundamenta a atividade antipsicótica, conforme esta, os sintomas positivos estariam relacionados a níveis elevados de dopamina na via mesolímbica, enquanto os sintomas negativos e cognitivos,possivelmente estão associados a níveis diminuídos desse neurotransmissor na viamesocortical. Os antipsicóticos cessam os sintomas da esquizofrenia, no entanto, 40% dospacientes permanecem resistentes (refratários) ao tratamento. Os pacientes com esquizofreniarefratária ao tratamento apresentam menor capacidade de síntese de dopamina do que aquelescom boa resposta aos antipsicóticos de primeira geração, sendo que uma adequada resposta aotratamento medicamentoso coincidi com uma maior densidade de sinapses dopaminérgicas,isto subsidia uma base biológica para a refratariedade. O polimorfismo de nucleotídeo simplesé uma variação da sequência de DNA devido a uma única diferença de nucleotídeos entre osalelos. Alguns deles podem ter efeitos funcionais e podem alterar a regulação positiva da expressão do receptor induzida por dopamina. Três principais destes polimorfismos foramabordados neste estudo: rs1800497, rs1799732 e rs6280. Objetivo: investigar a frequência dospolimorfismos rs1800497, rs1799732 e rs6280 e a ocorrência da esquizofrenia refratária

Introduction: Schizophrenia is considered one of the most severe and complex mentaldisorders that affect both the quality of life of the individual living with the disease and that ofhis family. It is characterized mainly by symptoms denominated positive (alteration in thethought process, perceptions and affection) and negative (affective-volitional blunting,cognitive losses and depressive symptoms). The risk factors for this disorder areepiphenomena of pathophysiological processes that result from a gene-environmentinteraction still poorly understood. The hypothesis of dopamine is the main conceptunderlying antipsychotic activity, as this, positive symptoms would be related to elevateddopamine levels in the mesolimbic pathway, while negative and cognitive symptoms arepossibly associated with decreased levels of this neurotransmitter in the mesocorticalpathway. Antipsychotics cease the symptoms of schizophrenia, however, 40% of patientsremain resistant (refractory) to treatment. Patients with treatment-refractory schizophreniahave a lower capacity for dopamine synthesis than those with a good response to first-generation antipsychotics, and an adequate response to drug treatment coincided with a higherdensity of dopaminergic synapses, this subsidizes a biological basis for refractoriness. Singlenucleotide polymorphism is a variation of the DNA sequence due to a single nucleotidedifference between the alleles. Some of them may have functional effects and may alter thepositive regulation of dopamine-induced receptor expression. Three major of thesepolymorphisms were addressed in this study: rs1800497, rs1799732 and rs6280. Objective:to investigate the frequency of polymorphisms rs1800497, rs1799732 and rs6280 and theoccurrence of refractory schizophrenia

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.

Nicergoline improves the depressive behavior of vascular depression in rats by regulating monoamine neurotransmitter receptors expression in hippocampal CA1 region and serum apolipoprotein E4 level / 国际脑血管病杂志

Objective To investigate the effects of nicergoline on expressions of 5-hydroxytryptamine 1A receptor (5-HT1AR), D2 dopamine receptor (D2DR),α2A adrenaline receptor (α2AAR) in the hippocampal CA1 region and the serum level of apolipoprotein E4 (ApoE4) in a rat model of vascular depression (VD) . Methods Forty-eight male Sprague-Daw ley rats w ere randomly al ocated into a normal control group, a model group, fluoxetine group, a low-dose nicergoline group, a medium-dose nicergoline group, and a nicergoline high-dose group ( n=8 in each group). A rat model of VD w as induced by the ligation of bilateral common carotid arteries combined w ith chronic unpredictable mild stress (CUMS) plus single housing. The rats did not conduct CUMS or single housing in the normal control group, and the rats in the model group conducted CUMS and single housing. The rats in the fluoxetine group w ere given fluoxetine 1.3 mg/(kg· d) for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The rats in the low -, medium-and high-dose nicergoline groups w ere given nicergoline 0.9, 1.9 and 3.8 mg/(kg· d), respectively for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The normal control group and the model group w ere given equal volume of distil ed w ater for gastric lavage, once a day for 3 w eeks. Depression-like behavior w as evaluated using sucrose solution consumption and open-field test. Immunohistochemical staining and Western blot were used to detect the expressions of 5-HT1AR, D2DR, andα2AAR in the hippocampal CA1 region. Enzyme linked immunosorbent assay w as used to detect serum ApoE4 level. Results Before CUMS, the scores of horizontal and vertical movement and sucrose solution consumption in the model group, the fluoxetine group and each nicergoline group w ere decreased significantly compared w ith the normal control group (al P<0.01);w hile at 21 days after CUMS, those in the fluoxetine group and the nicergoline medium-and high-dose groups w ere significantly higher than those in the model group (al P<0.05). There w ere no significant differences betw een the fluoxetine group and each nicergoline group. The expression levels of 5-HT1A R, D2DR, α2A AR, and the serum ApoE4 in the model group, the fluoxetine group, and each nicergoline group w ere significantly higher than those in the normal control group. Those of the fluoxetine group and the nicergoline medium -and high-dose groups were significantly lower than the model group (al P<0.01), while there were no significant differences betw een the fluoxetine group and each nicergoline group. Conclusions Nicergoline can improve the depression-like behavior in VD rats. Its mechanism may be associated w ith the dow nregulation of 5-HT1AR, D2DR, α2AAR expressions and serum ApoE4 level.

Functional Regulation of Dopamine D₃ Receptor through Interaction with PICK1

PICK1, a PDZ domain-containing protein, is known to increase the reuptake activities of dopamine transporters by increasing their expressions on the cell surface. Here, we report a direct and functional interaction between PICK1 and dopamine D₃ receptors (D₃R), which act as autoreceptors to negatively regulate dopaminergic neurons. PICK1 colocalized with both dopamine D₂ receptor (D₂R) and D₃R in clusters but exerted different functional influences on them. The cell surface expression, agonist affinity, endocytosis, and signaling of D₂R were unaffected by the coexpression of PICK1. On the other hand, the surface expression and tolerance of D₃R were inhibited by the coexpression of PICK1. These findings show that PICK1 exerts multiple effects on D₃R functions.

Roles of Dopamine D₂ Receptor Subregions in Interactions with β-Arrestin2

β-Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of β-arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with β-arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with β-arrestin2. For this, we employed dopamine D₂ and D₃ receptors (D₂R and D₃R, respectively), since they display distinct agonist-induced interactions with β-arrestins. Our results showed that the second and third intracellular loops of D₂R are involved in the agonist-induced translocation of β-arrestins toward plasma membranes. In contrast, the N- and C-termini of D₂R exerted negative effects on the basal interaction with β-arrestins.

Abundant immunohistochemical expression of dopamine D2 receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence

Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D2 receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D2 receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D2 receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D2 receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas.

Role of spinal dopamine D2 receptors in a rat model of neuropathic pain / 中华麻醉学杂志

Objective To evaluate the role of spinal dopamine D2 receptors in a rat model of neuropathic pain.Methods Thirty healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 180-200 g,wcre randomly divided into 5 groups (n =6 each) using a random number table:control group (group C),sham operation group (group S),neuropathic pain group (group NP),normal saline group (group N) and dopamine D2 receptor agonist quinpirole group (group Q).Neuropathic pain was produced by chronic constriction injury of the sciatic nerve (CCI) in rats anesthetized with intraperitoneal 2％ pentobarbital sodium 40 mg/kg.At 7 days after CCI,normal saline 10 μl was injected intrathecally over 30 s in group N,and quinpirole 10 μg (in 10 μl of normal saline) was injected intrathecally over 30 s in group Q.At 1 day before CCI,3 and 7 days aher CCI,and 30 min and 1,2,4,8 and 16 h after administration,mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.Results There was no significant difference in MWT and TWL at each time point between group C and group S.MWT was significantly lower,and TWL was shorter at T1-8 in NP,N and Q groups than in C and S groups.Compared with group N,no significant change was found in MWT and TWL at each time point in N group,and MWT was significantly increased,and TWL was prolonged at T4-6 in group Q.Conclusion Inhibited function of spinal dopamine D2 receptors is involved in the maintenance of neuropathic pain in rats.

Effects of protocatechuic acid on expression of D2DR, iNOS, and TH in striatum and midbrain of Parkinson's disease model mice / 中草药

The aim of this paper is to investigate the effects of protocatechuic acid (PCA) on the expression of D2DR, iNOS, and TH in striatum and midbrain of Parkinson's disease (PD) mice induced by MPTP. C57BL brown mice were used as experimental animals and were injected with MPTP (25 mg/kg. d) for 7 d to build PD model mice. PCA (10 mg/kg. d) and Madopar (125 mg/kg. d) had been ip administered to the PD mice for the precaution and treatment at the first and lasted for 7 d. The expression of D2DR, iNOS, and TH in the striatum and midbrain of PD mice induced by MPTP was detected by Western blotting method. The results showed that iNOS expression increased while D2DR and TH expression decreased in the striatum and midbrain of MPTP-induced PD mice. However, PCA significantly decreased the expression of iNOS while obviously increased the expression of D2DR and TH in the striatum and midbrain of MPTP-induced PD mice. PCA has a neuroprotective effect on the PD mice induced by MPTP, and its protective effects on mice brain are achieved at least partly by increasing TH and D2DR expression while decreasing iNOS expression.

Pharmacological Effect of Panax ginseng Extract Standardized with Ginsenoside Rg3 on Mating Behavior of Male Rats Treated with Dopamine Antagonists.

Aim: The aim of this study was to evaluate the effects of Panax ginseng extract standardized with ginsenoside Rg3 (PGRg3) on the mating behavior of sexually active or inactive male rats treated with dopamine antagonists. Methodology: Animals were treated with PGRg3 (50,150 and 450mg/kgb.w) with or without dopamine antagonists. The penile erection, motor activity and stretching-yawning episode were evaluated in animals treated with PGRg3 alone or in combination with lisurode or SND 919. Testosterone and sperm counts were also evaluated in different treatment groups. Results: The results showed that (-) Eticlopride counteracted PGRg3-induced penile erection but not motor hyperactivity. PGRg3 treatment enhanced lisuride-induced behavioral effects. Moreover, PGRg3 plus SND 919 showed a marked stretching-yawning behavior compared to the animals received SND 919 alone. PGRg3 also succeeded to increase testosterone level and sperm count in a dose dependent fashion. Conclusion: It could be concluded that DAD2 receptors are involved in PGRg3-induced mating behavior and testicular function improvement. PGRg3 could be used to improve sexual function and mating behavior in people suffering from erectile dysfunction.

Lack of dopamine D2 receptor exacerbates MPTP-induced Parkinson's disease in mice / 第二军医大学学报

Results After MPTP injection, the animals had a significantly longer time in pole testing, a significantly decreased score in swimming test, and a significantly decreased number of TH-positive neurons in the substantia nigra of the midbrain (P < 0. 05 or P<0. 01). Moreover, the behavioral changes and the decrease of TH-positive neuron numbers in D2-/- mice were more significant than those in the WT mice(P< 0. 05 or P<0. 01).

Preparation and animal in vivo study of 131 I-nalepride as a dopamine D2 receptor imaging agent / 重庆医学

Objective To study the preparation of 131 I-nalepride and its characters in small animal in vivo ,and to evaluate the feasibility for its application in diagnosing neuropsychiatric disease .Methods s-5-(tributyltin)-N-[(1-ethyl-2-pyrrolidinyl) meth-yl]-2 ,3-dimethoxy-benzamide was used as the labeled precursor .The hydrogen peroxide method was adopted to label131 I-nalepride . The bio-distribution character test in ICR mice was performed .SD rats were performed the blocking experiment and the cerebral au-toradiography .Results The radiolabeled yield and radiochemical purity were over 95% .The results of the bio-distribution character test showed that the striatum had the highest uptake .The striatum to cerebellum uptake radio(ST/CB) reached 111 .87 at 4 h after injection and the maximum ST/CB value of 416 .97 at 12 h after injection .Regional brain autoradiography showed that the optical densities were significantly decreased from 7 .43 ± 0 .86 to 1 .07 ± 0 .18 after injection of 131 I-naleprid(P<0 .05) .These results indi-cated that 131 I-nalepride had specific binding to the dopamine D2 receptor .131 I-nalepride was rapidly uptaken by organs after injec-tion .The initial uptake in liver and kidney were higher and the % ID/g values were 14 .82 ± 3 .88 and 10 .28 ± 1 .65 receptively .The tracer was cleared out from the organ quite rapidly .Conclusion 131 I-nalepride has the high affinity and specificity to dopamine D2 receptor ,which could be used as the EPECT imaging agent of dopamine D2 receptors and as a tool drug to screen and evaluate the affinity of other antipsychotic agents to dopamine D2 receptors .

Effects of Jianpizhidong decoction on dopamine D2 receptor mRNA in striatum of tourette' s syndrome model mice / 中华行为医学与脑科学杂志

Objective To study the effects of traditional Chinese medicine of Jianpizhidong decoction on dopamine D2 receptor(DAD2R) mRNA in tourette syndrome (TS) model mice brain striatum,and provide the proof of neural biochemical for Jianpizhidong decoction in curing children TS.Methods 32 male ICR mice were divided randomly into control group,model group,Jianpizhidong decoction group and Tiapride group.Except control group,all mice in model group,Jianpizhidong decoction group and Tiapride group were made to TS models by intraperitoneal injection of 3,3'-iminodipropionitrile.The control gronp and model group were given normal saline,Jianpizhidong decoction group and Tiapride group were given corresponding drugs by intragastric administration respectively.Results The striatum DATmRNA expression of model group,Tiapride group,and traditional Chinese medicine group decreased(respectively(0.139 ± 0.013),(0.15 ± 0.021),(0.141 ± 0.019)) than that of control group (0.180 ± 0.028),and with 14.1％,3.0％ and 3.9％ down respectively.In model group DATmRNA expression was lower than control group (P ＜ 0.01).In model group DATmRNA expression was lower than Tiapride group (P＜ 0.01).In model group DATmRNA expression was lower than traditional Chinese medicine group (P＜0.01).In Tiapride group DATmRNA expression was lower than traditional Chinese medicine group (P ＜ 0.01).Conclusion The function of improving symptoms of TS by Jianpizhidongtang may be relate to inhibite DAD2R hypersensitization to enhance the activity of substantia nigra-striatum.

A Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for the Detection of DRD2 Polymorphisms

Background: The dopamine D2 receptor gene (DRD2) plays a role in many diseases such as schizophrenia, Parkinson’s disease, and addictive behaviour. Methods currently available for the detection of DRD2 polymorphisms are costly and cannot detect all 8 polymorphisms of our research interest simultaneously (Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, A-241G, and −141C Ins/Del). Therefore, we developed a nested multiplex polymerase chain reaction (PCR) for simultaneous detection of these polymorphisms. Methods: Genomic DNA was extracted from blood using standardised methods. Primers specific at the 3’-end for the polymorphic sites were designed. A two-step PCR method was developed. In the first PCR, a region from exon 3 to 4, exon 7, the promoter region, and the 3’-region of DRD2 were specifically amplified. The products were subsequently used as templates in the second PCR. Sequencing was performed to validate the test results. Results: Specific bands corresponding to the amplified product of interest were obtained. The method was reproducible and specific when used to genotype patients with schizophrenia. The amplified sequences showed 100% homology to the DRD2 sequence. Conclusion: The method was found to be simple, rapid, specific, and reproducible for the simultaneous detection of the DRD2 polymorphisms.

Central Nervous System Drug Evaluation Using Positron Emission Tomography

In conventional pharmacological research in the field of mental disorders, pharmacological effect and dose have been estimated by ethological approach and in vitro data of affinity to the site of action. In addition, the frequency of administration has been estimated from drug kinetics in blood. However, there is a problem regarding an objective index of drug effects in the living body. Furthermore, the possibility that the concentration of drug in blood does not necessarily reflect the drug kinetics in target organs has been pointed out. Positron emission tomography (PET) techniques have made progress for more than 20 years, and made it possible to measure the distribution and kinetics of small molecule components in living brain. In this article, we focused on rational drug dosing using receptor occupancy and proof-of-concept of drugs in the drug development process using PET.