中枢胆碱能系统对吗啡成瘾影响研究现状李

AdvancesinPsychologicalScience于摘要介绍了中枢胆碱能系统对吗啡成瘾的影响及其机制。研究结果表明，吗啡成瘾过程中伏隔核等脑区关键词分类号应。Tjn报道：用吗啡慢性处理的大鼠，在吗啡戒断后的天纹状皮层和Ac中Ach性吗啡处理之后AdvancesinPsychologicalScience于摘要介绍了中枢胆碱能系统对吗啡成瘾的影响及其机制。研究结果表明，吗啡成瘾过程中伏隔核等脑区关键词分类号应。Tjn报道：用吗啡慢性处理的大鼠，在吗啡戒断后的天纹状皮层和Ac中Ach性吗啡处理之后ch这种适应性释放增加与轻度但接受腹侧中脑A神经元调节的纹状皮层和c胆碱能神经元活动增强，或许代表了吗啡的长久的神经适应性效应，并在与滥用药物的易感性增强相联[3。Ach的浓度；相反，把阿片抑制剂methylnaloxonium注入NAc则使NAc细胞间Ach的碱导致NAc细胞间Ach释放量迅速下降，1小时后枢胆碱能系统对吗啡成瘾的影响受到了人们的关1吗啡等药物成瘾过程中伏隔核等部位细伏隔核（nucleusaccumbensNac）被认为在阿*北京市教委科技发展计划项目（KM200710028021）资助。通讯作者：李新旺，E-mail:pro_xwli@--腹侧被盖区（ventraltegmentalarea，VTA）注射毒射对条件行为偏好的建立无效的剂量的吗啡（0.5导致的CPP[14]。Lu等人研究发现，外周注射胆碱能受体抑制剂东莨菪碱能够抑制吗啡诱导的的表达[15a等人的研究结果显示，东莨菪碱能够抑制吗啡诱导的行为敏感化的发展[1东莨菪碱能够抑制吗啡诱导的行为敏感化的发展；然而，进一步的研究显示，东莨菪碱不能抑制吗啡[17。这些结果说明东莨菪碱对吗啡诱导的成瘾行为具有一定程度的抑制作用。扁豆碱或者烟碱对吗CPP的强化作用[13。Zarrindast也发现，杏仁核注射阿托品抑制了吗啡强迫学习，乙酰胆碱对Morris水迷宫任务这类强迫研究发现，吗啡能够干扰大鼠对Morris水迷CPP）是动物研究中常用的行为指标。Takatoshi等NAcCPP模型中对吗啡的强化（negativereinforcement）；同时，这种去除NAc胆碱能细胞的小鼠注射可卡因所诱导的行为敏donepezilgalanthamine，能够非常显著地抑制吗啡和可卡因诱导的CPP以及自发活动；去除NAc[8]。Nakanishi（2003）也报道，使用免疫毒素介胆碱能激动剂和抑制剂对吗啡等成瘾行致的CPP以及可卡因激发的自发活动。Ninkovic发-2008剂氧化震颤素或胆碱酯酶抑制剂毒扁豆碱所反转[18,19]。Ukai等人研究显示，吗啡等阿片样物质对记-2008剂氧化震颤素或胆碱酯酶抑制剂毒扁豆碱所反转[18,19]。Ukai等人研究显示，吗啡等阿片样物质对记DA水平下降DA水平升高有关，而戒断期间伴NAcDA水平降低相联系。由此可NAcDA能在尾状核和NAc，多巴胺D2受体激动剂能够抑制Ach的释放[25]。另一方面，胆碱能系统也能够影响NAcDA释放。Tzavara等人通过转基因技术制备了胆碱能M4受体缺失小鼠（M4knockout,M4KO）。研究发现，M4KONAcDA释放水平及其代谢匹配小鼠；同时，M4KO小鼠对安非他明的敏感化增强。在中脑内部，M4受体位于胆碱能中间神经元GABA能传入神经元上。正常情况下，来自背侧AchM4受体，直接NAcDA神经元，或者间接通过抑制D1NAcDAM4KOM4Ach对投射到NAcDA神经元的自动抑制功能丧失，强化了中DANAc的兴奋输入[26]NAc中DA水平升高，提高了吗啡的成瘾效应。4把M5受体反义寡核苷酸注射到VTA的多巴胺区微量注射降低M5受体功能的反义寡核苷酸康定鑫等人发现，对吗啡建立起稳定的P的大鼠，VTA内神经型一氧化氮合酶阳性神经元表达5反义寡脱氧核苷酸则能够抑制吗啡诱导的P，同时也显著减少了A内OSCP次注射5反义寡脱氧核苷酸也可以逆转大鼠对伴A内NS表达[22。酸；吗啡依赖大鼠蓝斑核内nNOS表达增加，用纳NAc细胞间DA水平提高，-Ach释放下降；但是，使用吗啡多次处理之后，担Ach释放增加[27]。另外，使用吗啡处理能够增加中-Ach释放下降；但是，使用吗啡多次处理之后，担Ach释放增加[27]。另外，使用吗啡处理能够增加中基底部胆碱能神经元胞体或者树突上的突触后胆碱能系统通过与DA能系统的交互作用影响吗啡成瘾在行为敏感化动物模型上获得了直接证DAAch的调节：DA对其具有兴奋作用而Ach则抑制其功能。也就是说，纹状体NAc等脑区Ach释放减少、DA增加影响行为DA释放增加而引较小剂量的毒扁豆碱（0.1mg/kg）慢性处理对这种-2008preclinicalstudies.Psychopharmacology,2000,151:6RadaP,KristinJ,BartleyG.Hoebel.Effectsofnicotineandmecamylamine-inducedwithdrawalonextracellulardopamineandacetylcholineintheratnucleusaccumbens.Psychopharmacology,2001,157:6能系统就可能成为治疗阿片类药物成瘾的靶位之-2008preclinicalstudies.Psychopharmacology,2000,151:6RadaP,KristinJ,BartleyG.Hoebel.Effectsofnicotineandmecamylamine-inducedwithdrawalonextracellulardopamineandacetylcholineintheratnucleusaccumbens.Psychopharmacology,2001,157:6能系统就可能成为治疗阿片类药物成瘾的靶位之7RadaP,HoebelBG.Acetylcholineintheaccumbensisdecreasedbydiazepamandincreasedbybenzodiazepinewithdrawal:apossiblemechanismfordependency.EuropeanJournalofPharmacology,2005,508(1-3):131~138TakatoshiH,YasujiK,IraP,ShigetadaN.Acetylcholineenhancementinthenucleusaccumbenspreventsaddictivebehaviorsofcocaineandmorphine.ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica,2003,100:8NakanishiS,KanekoS,HikidaT.Roleofsynapticintegrationofdopaminergicandcholinergictransmissioninbasalgangliafunction.InternationalCongressSeries,2003,1250:487~492NinkovicJ,FolchertA,MakhankovYV,etal.GeneticidentificationofAChEasapositivemodulatorofaddictiontothepsychostimulantD-amphetamineinzebrafish.JournalofNeurobiology,2006,66(5):463~475.李新旺,徐爱红,于斌等.毒扁豆碱对吗啡导致的大鼠行为敏感化的抑制作用.心理学报,2005,37(3):362~365RezayofA,ZataliH,Haeri-RohaniA.Dorsalhippocampalmuscarinicandnicotinicreceptorsareinvolvedinmediatingmorphinereward.BehavioralBrainResearch,2006,166(2):RezayofA,Nazari-SerenjehF,ZarrindastMR.Morphine-inducedplacepreference:Involvementofcholinergicreceptorsoftheventraltegmentalarea.EuropeanJournalofPharmacology,2007,562(1/2):92~102ZarrindastMR,FattahiZ,RostamiP,RezayofA.RoleofcholinergicsystemintheratbasolateralamygdalaFišerováM,ConsoloS,KršiakM.Chronicmorphineinduceslong-lastingchangesinacetylcholinereleaseinratnucleusaccumbenscoreandshell:aninvivomicrodialysisstudy.Psychopharmacology,1999,142:85~94OsmanNI,BaghdoyanHA,LydicR.Morphineinhibitsacetylcholinereleaseinratprefrontalcortexwhendeliveredsystemicallyorbymicrodialysistobasalforebrain.Anesthesiology,2005,103(4):779~787TjonGH,DeVriesTJ,NestbyP,WardehG,MulderAH,SchoffelmeerAN.Intermittentandchronicmorphinetreatmentinduceslong-lastingchangesindelta-opioidreceptor-Pharmacology,Biochemistry&Behavior,2005,82(1):1~1015LuL,Nan-JieXuXG,YueW,etal.Reactivationofmorphineconditionedplacepreferencebydrugpriming:roleofenvironmentalcuesandsensitization.Psychopharmacology,2002,OkaT,HosoyaE.Effectsofhumoralmodulatorsandnaloxoneonmorphine-inducedchangesinthespontaneouslocomotoractivityoftherat.Psychopharmacology(Berl),1976,47(3):李新旺,徐爱红,.东莨菪碱对吗啡诱导的行为敏感化的影响.心理学报，2007，39(2):299~305LiZ,WuCF,PeiG,XuNJ.Reversalofmorphine-inducedmemoryimpairmentinmicebywithdrawalinMorriswatermazepossibleinvolvementofcholinergicsystem.Pharmacology,BiochemistryandBehavior,2001,68:507~513JafariMR,ZarrindastMR,DjahanguiriB.Influencecholinergicsystemmodulatorsonmorphinestate-acetylcholinereleaseinratstriatumandEuropeanjournalofpharmacology,1995,283(1-3):169~176RadaPV,MarkGP,TaylorKnucleus4etal.Morphinen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