中樞膽堿能系統(tǒng)對(duì)嗎啡成癮影響研究現(xiàn)狀李

AdvancesinPsychologicalScience于摘要介紹了中樞膽堿能系統(tǒng)對(duì)嗎啡成癮的影響及其機(jī)制。研究結(jié)果表明，嗎啡成癮過(guò)程中伏隔核等腦區(qū)關(guān)鍵詞分類(lèi)號(hào)應(yīng)。Tjn報(bào)道：用嗎啡慢性處理的大鼠，在嗎啡戒斷后的天紋狀皮層和Ac中Ach性嗎啡處理之后AdvancesinPsychologicalScience于摘要介紹了中樞膽堿能系統(tǒng)對(duì)嗎啡成癮的影響及其機(jī)制。研究結(jié)果表明，嗎啡成癮過(guò)程中伏隔核等腦區(qū)關(guān)鍵詞分類(lèi)號(hào)應(yīng)。Tjn報(bào)道：用嗎啡慢性處理的大鼠，在嗎啡戒斷后的天紋狀皮層和Ac中Ach性嗎啡處理之后ch這種適應(yīng)性釋放增加與輕度但接受腹側(cè)中腦A神經(jīng)元調(diào)節(jié)的紋狀皮層和c膽堿能神經(jīng)元活動(dòng)增強(qiáng)，或許代表了嗎啡的長(zhǎng)久的神經(jīng)適應(yīng)性效應(yīng)，并在與濫用藥物的易感性增強(qiáng)相聯(lián)[3。Ach的濃度；相反，把阿片抑制劑methylnaloxonium注入NAc則使NAc細(xì)胞間Ach的堿導(dǎo)致NAc細(xì)胞間Ach釋放量迅速下降，1小時(shí)后樞膽堿能系統(tǒng)對(duì)嗎啡成癮的影響受到了人們的關(guān)1嗎啡等藥物成癮過(guò)程中伏隔核等部位細(xì)伏隔核（nucleusaccumbensNac）被認(rèn)為在阿*北京市教委科技發(fā)展計(jì)劃項(xiàng)目（KM200710028021）資助。通訊作者：李新旺，E-mail:pro_xwli@--腹側(cè)被蓋區(qū)（ventraltegmentalarea，VTA）注射毒射對(duì)條件行為偏好的建立無(wú)效的劑量的嗎啡（0.5導(dǎo)致的CPP[14]。Lu等人研究發(fā)現(xiàn)，外周注射膽堿能受體抑制劑東莨菪堿能夠抑制嗎啡誘導(dǎo)的的表達(dá)[15a等人的研究結(jié)果顯示，東莨菪堿能夠抑制嗎啡誘導(dǎo)的行為敏感化的發(fā)展[1東莨菪堿能夠抑制嗎啡誘導(dǎo)的行為敏感化的發(fā)展；然而，進(jìn)一步的研究顯示，東莨菪堿不能抑制嗎啡[17。這些結(jié)果說(shuō)明東莨菪堿對(duì)嗎啡誘導(dǎo)的成癮行為具有一定程度的抑制作用。扁豆堿或者煙堿對(duì)嗎CPP的強(qiáng)化作用[13。Zarrindast也發(fā)現(xiàn)，杏仁核注射阿托品抑制了嗎啡強(qiáng)迫學(xué)習(xí)，乙酰膽堿對(duì)Morris水迷宮任務(wù)這類(lèi)強(qiáng)迫研究發(fā)現(xiàn)，嗎啡能夠干擾大鼠對(duì)Morris水迷CPP）是動(dòng)物研究中常用的行為指標(biāo)。Takatoshi等NAcCPP模型中對(duì)嗎啡的強(qiáng)化（negativereinforcement）；同時(shí)，這種去除NAc膽堿能細(xì)胞的小鼠注射可卡因所誘導(dǎo)的行為敏donepezilgalanthamine，能夠非常顯著地抑制嗎啡和可卡因誘導(dǎo)的CPP以及自發(fā)活動(dòng)；去除NAc[8]。Nakanishi（2003）也報(bào)道，使用免疫毒素介膽堿能激動(dòng)劑和抑制劑對(duì)嗎啡等成癮行致的CPP以及可卡因激發(fā)的自發(fā)活動(dòng)。Ninkovic發(fā)-2008劑氧化震顫素或膽堿酯酶抑制劑毒扁豆堿所反轉(zhuǎn)[18,19]。Ukai等人研究顯示，嗎啡等阿片樣物質(zhì)對(duì)記-2008劑氧化震顫素或膽堿酯酶抑制劑毒扁豆堿所反轉(zhuǎn)[18,19]。Ukai等人研究顯示，嗎啡等阿片樣物質(zhì)對(duì)記DA水平下降DA水平升高有關(guān)，而戒斷期間伴NAcDA水平降低相聯(lián)系。由此可NAcDA能在尾狀核和NAc，多巴胺D2受體激動(dòng)劑能夠抑制Ach的釋放[25]。另一方面，膽堿能系統(tǒng)也能夠影響NAcDA釋放。Tzavara等人通過(guò)轉(zhuǎn)基因技術(shù)制備了膽堿能M4受體缺失小鼠（M4knockout,M4KO）。研究發(fā)現(xiàn)，M4KONAcDA釋放水平及其代謝匹配小鼠；同時(shí)，M4KO小鼠對(duì)安非他明的敏感化增強(qiáng)。在中腦內(nèi)部，M4受體位于膽堿能中間神經(jīng)元GABA能傳入神經(jīng)元上。正常情況下，來(lái)自背側(cè)AchM4受體，直接NAcDA神經(jīng)元，或者間接通過(guò)抑制D1NAcDAM4KOM4Ach對(duì)投射到NAcDA神經(jīng)元的自動(dòng)抑制功能喪失，強(qiáng)化了中DANAc的興奮輸入[26]NAc中DA水平升高，提高了嗎啡的成癮效應(yīng)。4把M5受體反義寡核苷酸注射到VTA的多巴胺區(qū)微量注射降低M5受體功能的反義寡核苷酸康定鑫等人發(fā)現(xiàn)，對(duì)嗎啡建立起穩(wěn)定的P的大鼠，VTA內(nèi)神經(jīng)型一氧化氮合酶陽(yáng)性神經(jīng)元表達(dá)5反義寡脫氧核苷酸則能夠抑制嗎啡誘導(dǎo)的P，同時(shí)也顯著減少了A內(nèi)OSCP次注射5反義寡脫氧核苷酸也可以逆轉(zhuǎn)大鼠對(duì)伴A內(nèi)NS表達(dá)[22。酸；嗎啡依賴大鼠藍(lán)斑核內(nèi)nNOS表達(dá)增加，用納NAc細(xì)胞間DA水平提高，-Ach釋放下降；但是，使用嗎啡多次處理之后，擔(dān)Ach釋放增加[27]。另外，使用嗎啡處理能夠增加中-Ach釋放下降；但是，使用嗎啡多次處理之后，擔(dān)Ach釋放增加[27]。另外，使用嗎啡處理能夠增加中基底部膽堿能神經(jīng)元胞體或者樹(shù)突上的突觸后膽堿能系統(tǒng)通過(guò)與DA能系統(tǒng)的交互作用影響嗎啡成癮在行為敏感化動(dòng)物模型上獲得了直接證DAAch的調(diào)節(jié)：DA對(duì)其具有興奮作用而Ach則抑制其功能。也就是說(shuō)，紋狀體NAc等腦區(qū)Ach釋放減少、DA增加影響行為DA釋放增加而引較小劑量的毒扁豆堿（0.1mg/kg）慢性處理對(duì)這種-2008preclinicalstudies.Psychopharmacology,2000,151:6RadaP,KristinJ,BartleyG.Hoebel.Effectsofnicotineandmecamylamine-inducedwithdrawalonextracellulardopamineandacetylcholineintheratnucleusaccumbens.Psychopharmacology,2001,157:6能系統(tǒng)就可能成為治療阿片類(lèi)藥物成癮的靶位之-2008preclinicalstudies.Psychopharmacology,2000,151:6RadaP,KristinJ,BartleyG.Hoebel.Effectsofnicotineandmecamylamine-inducedwithdrawalonextracellulardopamineandacetylcholineintheratnucleusaccumbens.Psychopharmacology,2001,157:6能系統(tǒng)就可能成為治療阿片類(lèi)藥物成癮的靶位之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,徐愛(ài)紅,于斌等.毒扁豆堿對(duì)嗎啡導(dǎo)致的大鼠行為敏感化的抑制作用.心理學(xué)報(bào),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.RoleofcholinergicsystemintheratbasolateralamygdalaFi?erováM,ConsoloS,Kr?iakM.Chronicmorphineinduceslong-lastingchangesinacetylcholinereleaseinratnucleusaccumbenscoreandshell:aninvivomicrodialysisstudy.Psychopharmacology,1999,142:85~94OsmanNI,BaghdoyanHA,LydicR.Morphineinhibitsacetylcholinereleaseinratprefrontalcortexwhendeliveredsystemicallyorbymicrodialysistobasalforebrain.Anesthesiology,2005,103(4):779~787TjonGH,DeVriesTJ,NestbyP,WardehG,MulderAH,Schoffelm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