Methamphetamine Self-Administration Is Associated with Persistent Biochemical Alterations in Striatal and Cortical Dopaminergic Terminals in the Rat 英文参考文献.docVIP

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Methamphetamine Self-Administration Is Associated with Persistent Biochemical Alterations in Striatal and Cortical Dopaminergic Terminals in the Rat 英文参考文献.doc

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Methamphetamine Self-Administration Is Associated with Persistent Biochemical Alterations in Striatal and Cortical Dopaminergic Terminals in the Rat 英文参考文献

MethamphetamineSelf-AdministrationIsAssociated withPersistentBiochemicalAlterationsinStriataland CorticalDopaminergicTerminalsintheRat IrinaN.Krasnova1.,ZuzanaJustinova1,2.,BruceLadenheim1,SubramaniamJayanthi1,MichaelT. McCoy1,ChanelBarnes1,JohnE.Warner1,StevenR.Goldberg1,JeanLudCadet1* 1NationalInstituteonDrugAbuse,NationalInstitutesofHealth,Baltimore,Maryland,UnitedStatesofAmerica,2DepartmentofPsychiatry,UniversityofMarylandSchool ofMedicine,Baltimore,Maryland,UnitedStatesofAmerica Abstract Methamphetamine(meth)isanillicitpsychostimulantthatisabusedthroughouttheworld.Repeatedpassiveinjectionsof thedruggiveninasingledayoroverafewdayscausesignificantandlong-termdepletionofdopamineandserotoninin themammalianbrain.Becausemethself-administrationmaybettermimicsomeaspectsofhumandrug-takingbehaviors, weexaminedtowhatextentthispatternofdrugtreatmentmightalsoresultindamagetomonoaminergicsystemsinthe brain.Ratswereallowedtointravenouslyself-administermeth(yokedcontrolratsreceivedvehicle)15hoursperdayfor8 daysbeforebeingeuthanizedateither24hoursorat7and14daysaftercessationofdrugtaking.Methself-administration by the rats was associated with a progressive escalation of daily drug intake to 14mg/kg per day. Animals that self- administered meth exhibited dose-dependent decreases in striatal dopamine levels during the period of observation. In addition,thereweresignificantreductionsinthelevelsofstriataldopaminetransporterandtyrosinehydroxylaseproteins. There were also significant decreases in the levels of dopamine, dopamine transporter, and tyrosine hydroxylase in the cortex.Incontrast,methself-administrationcausedonlytransientdecreasesinnorepinephrineandserotoninlevelsinthe twobrainregions,withthesevaluesreturningtonormalatsevendaysaftercessationofdrugtaking.Importantly,methself- administrationwasassociatedwithsignificantdose-dependentincreasesinglialfibrillaryacidicproteininbothstriatumand cortex,withthesechangesbeingofgreatermagnitudeinthestriatum.Theseresultssuggestthatmethse