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第二十次全国儿科中西医结合学术会议

作者： WU Min Gao Ge Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Objectives:dysfunctional dopamine d2 Receptor(dRd2) may play a role in the pathophysiology of *** study aimed to explore the role of dopamine d2 Receptor(dRd2) in an IdPN mouse model of Td by Micro-PET/CT,Real-Time PCR and Western blotting Methods:Sd male rats were randomly divided into control(CG) and experimental(EG) groups(n=6).We simultaneously measured the density and brain distribution of dopamine d2 receptors(d2-Rs) by Micro-PE andWestern blotting;in addition,mRNA expression of d2-Rs was assessed by real time ***,glucose metabolism was evaluated in both ***:The expression of dopamine d2-like receptor d2(dRd2) in the striatum was significantly decreased both at the mRNA and protein *** findings were confirmed by the Micro-PET *** addition,cerebral glucose metabolism was increased in IdPN mice compared with the control group(CG).Conclusions:These findings indicate that decreased dRd2 expression in the striatum may be involved in the pathogenesis of Tourette syndrome.

关键词： Tic disorders dopamine d2 receptors Micro-PET/CT Real-Time RT-PCR Western blotting Immunohistochemistry

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dopamine d2 receptor and sleep-wake regulation

Dopamine D2 receptor and sleep-wake regulation

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中国神经科学学会第十届全国学术会议

作者： Zhi-Li Huang Wei-Min Qu department of Pharmacology Shanghai Medical CollegeFudan University State Key Laboratory of Medical Neurobiology Shanghai Medical CollegeFudan University The Institute of Brain Science Shanghai Medical CollegeFudan University

dopamine(dA) has been reported to regulate processes responsible for the generation of complex movements and emotions,cognition,reward processing,and drug ***,the role assigned to dA in sleep-wake regulation has been relatively *** main dA receptors(R) in the brain are dR and *** clarify the roles of dA receptors in the sleep-wake regulation,dR knock-out(KO) mice,selective gene deletion strategies based on focal RNA interference to silence the expression of dR,the human dR gene carried by AAV to focally rescue dR in dR KO mice,and pharmacological manipulation were *** found that the dR blockade could reduce the sleep latency and increase amounts of non-rapid eye movement(non-REM,NREM) *** is the most potent wake-promoting medicine for enhancing the extracellular dA level in the nucleus accumbens and the prefrontal cortex,and for increasing *** using dR KO mice and dR antagonist,we demonstrated that dR and dR are essential for the arousal effect of modafinil,with dR being the receptor of primary *** with wild-type(WT) mice,dR KO mice exhibited a significant decrease in *** the KO mice were subjected to a cage change,the latency to sleep in the KO mice decreased to half of the level for WT ***,focal RNA interference in WT mice and rescue technology for dR in the KO mice showed that dRs located in the core of NAc play more important role in promoting arousal and locomotion than other parts in the *** results indicate that dR plays an essential role in the maintenance of wakefulness.

关键词： dopamine d2 receptors sleep wakefulness AAV knockout

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Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its correlation with dA receptor subtypes

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Acta Pharmacologica Sinica 2004年第12期25卷 31-39页

作者： Yu FU2,3,4, Zi-tao ZHU2,5, Xing-zu ZHU2, Guo-zhang JIN2,6 2State KeyLaboratory of drug Research,Shanghai Institute ofMateria Medica, Shanghai Institutes for BiologicalSciences, ChineseAcademy of Sciences, Graduate Schoolof the Chinese Academy of Sciences, Shanghai 201203, ChinaNow in department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA,5Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA, 中科院上海生命科学院 State Key Laboratory of Drug ResearchChinese Academy of Sciences

AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the d1 agonist-d2 antago- nist action on meso-accumbens-mPFC dA system. METHOdS: Single unit spontaneous firing activity was re- corded in the nucleus accumbens (NAc) neurons of na?ve and unilateral-6-hydroxydopamine (6-OHdA)-lesioned Sprague-dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by the change of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced a decrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB-18 was capable of reversing the inhibition induced by both d2 agonist LY171555 and d1/d2 agonist APO on NAc firing activity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which was reversed by the d1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited by iontophoretically applied THPB-18 in 90 % of 6-OHdA-lesioned rats, while THPB-18 caused variable effects on the firing of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked by iontophoretic application of SCH23390, but not d2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine, THPB-18 also possesses the “d1 agonistic-d2 antagonistic” dual action on the VTA-NAc dA system.4Now in department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.5Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA,4Now in department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.5Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA,5Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA,

关键词： berberine dopamine d1 receptors dopamine d2 receptors nucleus accumbens

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Sympatho-inhibitory effects of γ-l-glutamyl-l-dopa are not mediated by activation of dopamine-2 receptors in conscious rabbits

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Acta Pharmacologica Sinica 1995年第3期16卷 3-7页

作者： Zhi-Qin WANG,Kazumasa SHIMIZU, diana WAY, John SECOMBE, Barry P McGRATH (University department of Medicine and departemnt of Clinical Biochemistry, Monash Medical Center, Melbourne, Victoria 3168, Australia) Monash Medical Center 澳大利亚

AIM: To define the role of dopamine-2 receptors in the sympatho-inhibitory effects of Y-l-glutamyl-l-dopa in conscious rabbits. METHOd: γ-l-glutamyl-l- dopa ( gludopa ) was infused iv at 25 and 100ug#·kg-1. min-1 with and without prior dopamine-2 receptor blockade by YM-09151-2 (50 ng·kg~1 iv) in conscious rabbits. RESULTS: Mean arterial pressure and heart rate remained unchanged while renal plasma flow increased. Arterial norepinephrine (NE) concentration, total and renal NE spillover rate were markedly decreased in a dose-related manner, which were not affected by prior dopamine-2 receptor blockade . Gludopa was detected in the whole brain (92+112 ng/g wet brain tissue) at the end of experiment although brain tissue lev-odopa, NE, and dopamine contents were not much different from those in the control group. CONCLUSION: Gludopa decreased dose-dependently plasma NE concentration, and total and renal NE overflow to plasma, which were not mediated by activation of dopamine d2 receptors.

关键词： dopamine d2 receptors dopamine gludopa levodopa norepinephrine sympathetic nervous system YM-09151-2

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