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Extracellular Signal-Regulated Kinase in Nucleus Accumbens Mediates Propofol Self-Administration in Rats

Neuroscience Bulletin 2016年第6期32卷 531-537页

作者： Benfu Wang Xiaowei Yang Anna Sun Lanman Xu Sicong Wang Wenxuan Lin Miaojun Lai Huaqiang Zhu Wenhua Zhou Qingquan Lian Department of Anesthesiology and Pain Medicine the Second Affiliated Hospital of Wenzhou Medical University Laboratory of Behavioral Neuroscience Ningbo Addiction Research and Treatment CenterSchool of MedicineNingbo University Department of Infection and Liver Diseases the First Affiliated Hospital of Wenzhou Medical University

Abstract Clinical and animal studies have indicated that propofol has potential for abuse, but the specific neurobi- ological mechanism underlying propofol reward is not fully understood. The purpose of this study was to inves- tigate the role of extracellular signal-regulated kinase （ERK） signal transduction pathways in the nucleus accumbens （NAc） in propofol self-administration. We tested the expression of p-ERK in the NAc following the maintenance of propofol self-administration in rats. We also assessed the effect of administration of SCH23390, an antagonist of the D1 dopamine receptor, on the expression of p-ERK in the NAc in propofol self-administering rats, and examined the effects of intra-NAc injection of U0126, an MEK inhibitor, on propofol reinforcement in rats. The results showed that the expression of p-ERK in the NAc increased significantly in rats maintained on propofol, and pre-treatment with SCH23390 inhibited the propofol self- administration and diminished the expression of p-ERK in the NAc. Moreover, intra-NAc injection of U0126 （4 μg/ side） attenuated the propofol self-administration. The data suggest that ERK signal transduction pathways coupledwith D1 dopamine receptors in the NAc may be involved in the maintenance of propofol self-administration and its rewarding effects.

关键词： dopamine receptor Drug reward ERK Anesthesiology Nucleus accumbens

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D2- like but not D1- like dopamine receptors in ventrolateral orbital cortex are involved in apomorphine-induced antiallodynia in a neuropathic pain model of rats

D2- like but not D1- like dopamine receptors in ventrolatera...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Yong-Hui DANG~1,Yan ZHAO~1,Bo XING~1,Xiao-Jie ZHAO~1,Teng CHEN~1,Jing-Shi TANG~2,Fu-Quan HUO~2,Feng-Yi XU~2, Chao-LingQU~(2,*) 1 Department of Forensic Medicine,Key Laboratory of Environment and Gene Related to Diseases,Ministry of Education, Xi''an Jiaotong University School of Medicine,Xi''an 710061,China 2 Department of Physiology and Pathophysiology,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education,Xi''an Jiaotong University School of Medicine,Xi''an 710061,China

＜正＞Objective The ventrolateral orbital cortex（VLO） is part of an endogenous analgesic system consisting of an ascending pathway from the spinal cord to VLO via the thalamic nucleus submedius（Sm） and a descending pathway to the spinal cord relaying in the periaqueductal gray（PAG）.The aim of the present study was to examine whether dopamine and its receptors are involved in the antinociception in *** The animal model of persistent peripheral neuropathic pain-spared nerve injury（SNI） was *** withdrawal threshold in response to von-Frey hair stimulation of the injury side hindpaw was measured as an index of mechanical ***（1） Microinjection of the nonselective dopamine receptor agonist apomorphine（1.0,2.5,5.0μg in 0.5μl） into the VLO significantly increased the paw withdrawal threshold in a dose-dependent manner,which was reversed by pretreatment with selective D2-like dopamine receptor antagonist raclopride（1.5μg in 0.5μl）,but not selective D1-like dopamine receptor antagonist（SCH23390 5.0μg in 0.5μl）.（2） Microinjection of raclopride or SCH23390 alone into the VLO had no effects on mechanical paw withdrawal threshold. Conclusion The results suggest that dopamine neurotransmitter is involved in VLO-induced anti-allodynia,and this effect is mediated by D2-like but not Dl-like dopamine receptors.

关键词： ventrolateral orbital cortex dopamine receptor raclopride SCH23390 mechanical allodynia spared nerve injury rat

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Apomorphine effects on the hippocampus

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Neural Regeneration Research 2018年第12期13卷 2064-2066页

作者： Luis Enrique Arroyo-García Antonio Rodríguez-Moreno Gonzalo Flores Laboratorio de Neuropsiquiatria Instituto de Fisiologia Benemerita Universidad Autenoma de Puebla Puebla Mexico Laboratorio de Neurociencia Celular y Plasticidad Universidad Pablo de Olavide Sevilla Spain

Apomorphine is a non-specific dopamine receptor agonist that has been used in the treatment of some diseases and mental disorders. Its use has particularly well documented in Parkinson＇s disease（PD）. The dopaminergic agonists like apomorphine are related to oxidative processes that could induce cell damage and the functional impairment of some structures in the brain. However, most information about apomorphine in literature is focused on the improvement of the motor problems characteristic of PD, but little is known about the effects on cognitive behaviors and brain structures indirectly related to motor function. The presence of dopaminergic receptors in the hippocampus has recently been discovered, in connection with cognitive behaviors like learning and memory, these receptors are needed in neuronal plasticity. There has been a growing interest to know if this structure could be compromised by the effect of apomorphine and elucidate if part of the cognitive impairment present in the PD is due to the effect of apomorphine. In this mini-review, we summarized how apomorphine has been used since its creation, we discuss the latest information about its effect on the hippocampus and also the future perspectives to fully understand the effects of this compound.

关键词： dopamine receptor apomorphine hippocampus learning and memory plasticity dendritic length oxidative stress Parkinson's disease

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Etiological characteristics and treatment of tardive dyskinesia

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Neural Regeneration Research 2006年第6期1卷 549-552页

作者： Zhe Li Xueli Sun Che Zhou Mental Health Center West China Hospital Sichuan University Chengdu 610041 Sichuan Province China

OBJECTIVE ： The pathogenesis of tardive dyskinesia （TD） is complicated and uncertain, Thus, there is not any effective treatment for it. The psychiatrists pay more and more attention to TD, which lasts for a long time and is difficult to treat. DATA SOURCES： A computer-based online search of Medline database was undertaken to identify articles about the feature of etiology and the progression of treatment for TD published in English by using the keywords of ＂rD, etiology, pathogenesis＂ and ＂TD, therapy, drug treatment＂. Meanwhile, Chinese articles about the feature of etiology and the progression of treatment for TD were searched in Wanfang database and China journal full-text database, and the keywords were ＂TD, etiology, pathogenesis＂ and ＂TD, therapy, drug Treatment＂ in Chinese. STUDY SELECTION： Articles met the following inclusion criteria were selected in this paper. Inclusion criteria：（1） Researches of randomized blind control design, before and after control design and retrospective. （2） Researches of the feature of etiology and the progression of treatment for TD. Exclusion criteria： the repetitive researches and individual reports. DATA EXTRACTION ： Totally 65 articles related the feature of etiology and the progression of treatment for TD of randomized blind control design, before and after control design and retrospective studies were collected, and 53 of them were accorded with the inclusion criteria. Of the 12 excluded ones, 8 were concerning with genetics, 4 were repetitive researches. DATA SYNTHESIS ： The feature of etiology for TD includes：（1） Hypothesis of dopamine receptor super-sensitivity： The dopamine receptor is persistently blocked, so it will result in functional disorder in CNS, and then TD may take place. （2）） Hypothesis of neuronal degeneration： The concentration of aminosuccinic acid and glutamic acid will increase after the antipsychotic used for a long time and this will result in neuronal degeneration through glutamic acid rec

关键词： dopamine receptor neuronal degeneration control design therapeutic effect free radicals radical scavenger gene polymorphism prevention of glutamic acid retrospective studies tardive dyskinesia cytotoxic effect corpus striatum calcium ions nerve cells amino acid vitamin E

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Modulation by Biogenic Amines for the Hemocyte Count and Prophenoloxidase Exocytosis via receptors in Litopenaeus vannamei

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Journal of Ocean University of China 2011年第4期10卷 425-432页

作者： PAN Luqing LIU Huijie YU Jinhong Department of Aquaculture the Key Laboratory of MaricultureMinistry of EducationOcean University of ChinaQingdao 266003P.R.China

Hemocyte counts and phenoloxidase(PO)activity were examined after hemolymph being incubated in dopamine(DA),noradrenaline(NE)and serotonin(5-HT).Results showed that all the three biogenic amines(BAs)had a significant impact on total hemocyte count(THC),differential hemocyte count(DHC),and intracelluar and extracelluar phenoloxidase(PO)*** these Bas,DA had the strongest effect on the above parameters,whereas 5-HT had the least *** with D1 receptor antagonist SCH23390,D2 receptor antagonist Sulpiride and 1:1 admixture of the two could significantly inhibit the effect of DA on these ***23390 showed a stronger inhibitory effect than Sulpiride,and the admixture exhibited the strongest *** results suggested that the change of hemocyte count and activation of prophenoloxidase(proPO)system in Litopenaeusvan-namei hemocyte can be regulated by BAs,and DA modulates the two parameters via its receptors.

关键词： biogenic amine dopamine receptor hemocyte Litopenaeus vannamei prophenoloxidase system

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I-Stepholidine increases the frequency of sEPSC via the activation of D1 dopamine signaling pathway in rat prelimbic cortical neurons

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Acta Pharmacologica Sinica 2007年第5期 627-633页

作者： Ming GAO Chang-liang LIU Shen YANG Xue-chu ZHEN Guo-zhang JIN Department of Pharmacology,State Key Laboratory of Drug Research,Institute of Materia Medica,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 201203,China

Aim:To investigate the effect of l-stepholidine (SPD) on the frequency of spon-taneous excitatory postsynaptic currents (sEPSC) in the pyramidal cells betweenlayers Ⅴ and Ⅵ in the prelimbic cortex (PL).Methods:A whole-cell patch clamp inrat brain slices was ***:SPD significantly increased the frequency ofsEPSC in a concentration-dependent manner.A selective D1dopamine receptorantagonist SCH23390 blocked SPD-mediated effects,whereas the D1agonistSKF38393,but not the D2/3antagonist sulpiride,mimicked SPD-mediated increasein the frequency of ***,both protein kinase A (PKA) inhibitor N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide hydrochloride andprotein kinase C (PKC) inhibitor chelerythrine attenuated the effect of SPD ***:SPD elicits its effect on the frequency of sEPSC on the PLpyramidal cells via presynaptic D1receptors,and is dependent on PKA and PKCsignaling pathways.

关键词： l-stepholidine prelimbic cortex whole-cell patch clamp spontaneous excitatory postsynaptic currents dopamine receptor

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A STUDY OF CRYSTAL STRUCTURE OF TETRAHYDROPROTOBERBERINES AND EFFECTS ON DEPAMINE receptor D-1 AND D-2 SUBTYPES IN BRAIN

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Progress in Natural Science:Materials International 1991年第3期 247-252页

作者：吴吉安陈洁金国章林光大嵇汝运 PRC Shanghai 200031 Shanghai Institute of Biochemistry Shanghai Institute of Materia Medica Academia Sinica

The molecular structure of tetrahydroberberine(THB)is determined by X-ray diffraction *** the analysis of the crystal structure of four l-tetrahydroprotoberberines(l-THPB),i.e.l-tetrahydropalmatine(l-THP),l-corydalamine(l-CDL),l-stepholidine(l-SPD),l-THB and the QSARcalculation of Hansch approach,we find that the negative correlation exists between A-D ring dihedralangles of THPB crystal structures and the potency of the inhibition of D-1 and D-2 *** re-sults suggest that the smaller the A-D dihedral angle,the easier the binding to the DA *** cal-culation results also show that the activity of the l-THPB toward D-1 receptor is higher by 4.5—6.1times than that toward D-2 receptor.

关键词： X-ray diffraction dopamine receptor tetrahydroprotoberberine(THPB) quantitative structure-activity relationship(QSAR)

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l-Stepholidine targeting at D1/D2 receptors induces sleep in mice

l-Stepholidine targeting at D1/D2 receptors induces sleep in...

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2008年中国睡眠研究会第五届学术年会

作者：邱梅红黄志力 State Key Laboratory of Medical Neurobiology Shanghai Medical College of Fudan University Department of Pharmacology Shanghai Medical College of Fudan University

l-Stepholidine(SPD),an active ingredient of the Chinese herb Stephonia,is the first compound known to have mixed D agonist/D antagonist properties as potential treatment medications for *** elucidate whether SPD modulates the sleep-wake cycle,we observed the effects of SPD on sleep-wake cycles in mice through a highly efficient and stable mouse sleep bioassay *** results showed that SPD administrated *** 40 or 80 mg/kg significantly increased the total time spent in sleep during dark period, and prolonged durations of non-rapid eye movement(NREM)sleep episodes,with a concomitant reduction in amount of *** only at dose of 80 mg/kg,SPD increased the number of state transitions from NREM sleep to wakefulness and,subsequently,from wakefulness to NREM *** rendered no effect on rapid eye movement(REM)***,the power density of NREM and REM sleep both were not *** study showed that c-Fos expression in the ventrolateral preoptic area was significantly increased by SPD administration in a dose-dependent manner,compared with that of vehicle *** results indicated that SPD induced NREM sleep in mice,which may be mediated by activating the ventrolateral preoptic area,suggesting its potential application for treatment of insomnia.

关键词： l-stepholidine Sleep dopamine receptor Electroencephalogram Mice

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A rodent model of NMD A receptor hypofunction for the study of schizophrenia

A rodent model of NMD A receptor hypofunction for the study ...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： TM du BOIS KA NEWELL K ZAVITSANOU Centre for Translational Neuroscience School of Health ScienceUniversity of WollongongAustralia

＜正＞Background NMDA receptor antagonist potently elicits symptoms similar to those seeing in schizophrenia ***,it can disrupt brain development by increasing apoptosis and can cause behavioral alterations in later life. Purpose:The aim of this study was to investigate apoptosis,dopamine system and behavioural alterations in rats treated with phencyclidine（PCP） before or after brain *** In one experiment,apoptotic cells were quantified following PCP（10 mg/kg） treatment in perinatal,adolescent or adult *** another experiment,PCP was administered to female rat pups on postnatal day（PN）7,9 and *** PN12,18,32 and 96 brain tissue was collected for biochemical *** cohort of rats underwent behavioural testing 10 weeks after their last perinatal PCP *** Perinatal PCP treatment significantly increased the number of apoptotic cells primarily in cingulate and frontal *** contrast,adolescent and adult PCP treatment did not cause *** PCP treatment also caused a hyperdopaminergic state upon maturation as evidenced by increased tyrosine hydroxylase and dopamine transporter, and decreased D2 receptor expression in specific regions of the mesolimbic/striatal *** PCP-treated rats displayed increased spontaneous locomotion and increased climbing time in the forced swim *** This study has demonstrated that early brain development interruption by NMDA receptor antagonism can alter chemically coded neural network formation in the adult *** only mild behavioural alterations were found,it is likely that this early treatment has left the brain more susceptible to future challenges.

关键词： schizophrenia brain development dopamine receptor glutamate receptor behaviour

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SKF83959 stimulates Ca2+ signals in primary cultured hippocampal neurons

SKF83959 stimulates Ca2+ signals in primary cultured hippoca...

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第十五届国际药理学大会

作者： Lihong Long Yuling Ming Hai Zhang. Fang Wang. Jianguo Chen Xuechu Zhen. Department of Pharmacology. Tongji Medical College. Huazhong University of Science and Technology Wuhan 430030 China

＜正＞ The present work was to characterize the Ca2+ signal regulated by PI - linked D1 dopamine receptor agonist SKF83959 in primary cultured hippocampal neurons by calcium imaging. The results indicated that SKF83959 induced a long - lasting increase of basal [ Ca2 + ] i in a time - and dose - dependent manner. The sustained elevation of [Ca2+ ]i was depend on both intracellular Ca2+ release and Ca2+ influx. 1 μM thapsigargin abolished SKF83959 - induced stimulation of Ca2+ ,indicating that the initial phase of Ca2 + increase from intracellular stores triggered the late phase of Ca2 + influx. Activation of PLCβ/IP3 was responsible for the drug -induced Ca2 + release from intracellular stores. Both Cd2 + and nifedipine largely attenuated SKF83959 - induced [Ca2+ ]iincrease. 10 MM APV but not 10 μM CNQX reduced SKF83959 - induced late phase of[ Ca2+ ]i,indicating that L -type calcium channel and NMDA receptor channel contributed to PI - linked D1 receptor - regulated [Ca2+ ]i changes.

关键词： SKF83959 dopamine receptor Ca2+ signal

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