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:2008-07-08:(3040012);。:(1981-),(),,,Tel.024-23986341,E-mailqj8107@gmail.com;(1959-),(),,,,Tel.024-23986339,E-mailwucf@sy-phu.edu.cn。:1006-2858(2008)Z-0017-06,亓 佳,杨静玉,王 芳,吴春福(,110016):,,。41。,,,。:;;;:R96 :A (methamphetamine,MAP),,“”。。,。()、、、、,。MAP,,HIV,,[1-2]。,、、、、,21[3]。MAP。(,、,,,。。1 1.1 MAPMAP,,,,,。MAP,,,,,,,,,[4]。MAP,、。(),、、、,,MAP,:、(、)、、、。,。10mg·kg-124,。MAP(40mg·kg-1)(dopamine,DA),(serotine,5-HT)25200810 JournalofShenyangPharmaceuticalUniversityVol.25Suppl. Oct.2008p.17 ,DA,(GFAP),[5]。,,,[6]。VeronicaSandovalDA,,DA,24h,。,DAWIN35428,。,;,DA。,DAD1D2DA,[7]。YossefItzhakMAP,MAPDA,。MAP[8]。1.2 MAPMAP24h,HE,、、、,,。,,MAP;,,,MAP,、,;,,,,;,,,、,MAP。MAP,,[9]。2 ,、、,,、、。,,,。,。,Gaetano,[10]。。,。,、、、、(ventraltegmentalarea,VTA)、(nucleusaccumbens,NAc),、、。,(),DA。,。,。。。,,DA,5-HT,ACh,GABA,。2.1 DAA10。DA,NAc、、、、、;,。,。,。--(meso-corticolimbicdopaminergicsystem,MLDS)。,,,,,DA[11-12]。,18 25VTANAc,[13]。DA[14]。6-OHDA,。DA,DA60%～90%,[15]。DA。GABA,DA。、DA[16-17]。DADA,DA(DAT),DA,DA,[18-19]。2.2 5-,5-HT,5-HT3,、。,5-HT3。NAc5-HT3DA,5-HT3NAcDA[20]。5-HT。5-HT。2.3 、、,VTA,NAc。,。,,。,。VTANMDA、MK-801NMDA。NMDAMg2+,C(PKC),NMDAMg2+,NMDA,NMDA(NOS)[21]。。NAc,/[22],NAc。,(170%),GLT1,GLT1,GLT1,[23]。GluVTADA。Peakman,AMPAGIuR2NAc,GIuR2,。GABA,VTADAmPFC,。VTANAc、PFCDA。NMDAMK-801,。VTANMDAAMPA。,NMDAdextromethorphanacamprosate,、、。David,NMDAAMPAVTA,VTAGABADA[24]。NMDANMDAGABA,DA。mPFCNAcGABA,NMDAAMPANAcGABA,VTAVPGABADA。,VTANMDAAMPADA,NAcGABA。19 ,,,。,(LTP)。LTP,LTP,LTP;NMDA[25]。2.4 ,,,[26]。。[27]。3 ,,,。,、(,)(,)。、、。2003,129.1%(2100)()。,[28]。2。。,,,,,,95%[29-30]。,2,,。,,,,。。,。3.1 FrawleySmith,(),,。,,[31]。3.2 Galllloway,。,[32]。3.3 Matrix,,[33-34]。,。,,,[35-38]。,。,。,,[39-41]。,。:[1]FROSCHD,SHOPTAWS,HUBERA,etal.SexualHIVriskamonggayandbisexualmalemetham-phetamineabusers[J].JournalofSubstanceAbuseTreatment,1996,13:483-486.[2]NEEDLERH,COYLES,TROTTERR,etal.HIVriskbehaviorsassociatedwiththeinjectionprocess:Multipersonuseofdruginjectionequipmentandpara-phernaliaininjectiondrugusernetworks[J].Substance20 25Use&Misuse,1998,33:2403-2423.[3].[J].,1999,2:13-16.[4].[M].:,1999,2-12.[5]CAPPONGD,CUNFENGPU,VORHEESCV.Time-courseofmethamphetamine-inducedneuro-toxicityinratcaudate-putamenaftersingle-dosetreatment[J].BrainResearch,2000,863:106-111.[6]JOHNSON-DAVISKL,FLECKENSTEINAE,WILKINSDG.Theroleofhyperthermiaandmetabolismasmechanismsoftolerancetometham-phetamineneurotoxicity[J].EuropeanJournalofPhar-macology,2003,482:151-154.[7]SANDOVALV,HANSONGR,FLECKENSTEINAE.Methamphetaminedecreasesmousestriataldopaminetransporteractivity:rolesofhyperthermiaanddopamine[J].EuropeanJournalofPharmacology,2000,409:265-271.[8]ITZHAKY,MARTINJL,BLACKMD,etal.Effectofmelatoninonmethamphetamine-and1-methyl4-phenyl-1,2,3,6-tetrahydropyridine-induceddopaminergicneurotoxicityandmethamphetamine-inducedbehavioralsensitization[J].Neuropharmaco-logy,1998,37:781-791.[9]SEIDENLS,SABLOLKE.Methamphetamineandmethylenedioxymethamphetamineneurotoxicity:pos-siblemechanismsofcelldestruction[J].NIDARes,1996,163:251-276.[10]DIXHIARAF,NORTHRA.Neurobiologyofopiateabuse[J].TIPS,1991,13:185-193.[11],.[J].,1999,1:5-9.[12],,.-[J].,1994,3(2):76-78.[13]AMALRICM,CLINEEJ,MARTINEZJL,etal.Rewardingpropertiesofβ-wndorphinasmeasuredbyconditionedplacepreference[J].Psychopharmacology,1987,91:14-19.[14]AULISIEF,HOEBELBG.Rewardingeffectsofam-phetamineandcocaineinthenucleusaccumbensandblockbyflupenthixol[J].SocNeurosciAbstr,1983,9:121.[15]BAPTISTAT,TENEUDL,CONTRERASQ,etal.Hermandez.Effectsofacuteandchroniclithiumtreat-mentonamphetamine-induceddopamineincreaseinthenucleusaccumbensandTransmission-Gen[J].Sec,993,94:75-89.[16]WISERA,BOZARTHMA.Apsychomotortheoryofaddiction[J].PsycholRev,1987,94:469-492.[17]DICHIARAG,NORTHGA.Neurobiologyofopiateabuse[J].TrendsPharmacolSci,1992,13:185-193.[18],[J].,1993,2(3):159-163.[19]SEIDENLS,KLEVENMS.Methamphetamineandrelateddrugs:toxicityandresultingbehavioralchangedinresponsetopharmacologicalprobes.In:AsgharK,SouzzaED,eds.PharmacologyandToxicologyofAm-phetamineandRelatedDesignerDrugs.NIDAResMonogrSerNo94.Rockville:DHHSPublication,1989:68-126,146-160.[20]KALIVASPW.Neurotransmitterregulationofdopamineneuronsintheventraltegmentalarea[J].BrainResRev,1993,18:75-113.[21]BREDTDS,SNYDERSH.Nitricoxideanovelneu-ronalmessenger[J].Neuron,1992,8(1):3-11.[22]CHURCHILLL,SWANSONCJ,URBINAM,etal.Repeatedcocainealtersglutamatereceptorsubunitlev-elsinthenucleusaccumbensandventraltegmentalareaofratsthatdevelopbehavioralsensitization[J].JNeurochem,1999,72(6):2397-2403.[23]XUNJ,BAOL,FANHP,etal.MorphinewithdrawalincreasesglutamateuptakeandsurfaceexpressionofglutamatetransporterGLT1athippocampalsynapses[J].JNeurosci,2003,23(11):4775-4784.[24]DAVIDV,DURKINTP,CAZALAP.Rewardingef-fectsmatergicantagonistsintotheventraltegmentalarearevealedbyanintracranialself-administrationparadigminmice[J].EuropeanJournalofNeuro-science,1998,10:1394-1402.[25]XIECW,LEWISDV.Opioid-mediatedfacitationoflong-termpotentiationatthelateralperforantpath-dentategranulecellsynapse[J].JPharmacolExpTher,1991,256(1):289-296.[26]TAGUCHIK,ATOBEJ,MASATOSHIK,etal.Th