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NationalInstituteonDrugAbuse(NIDA)
TheBrain&theActionsofCocaine,OpioidsandMarijuana
LastUpdatedJanuary2007https://www.drugabuse.gov
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TableofContents
TheBrain&theActionsofCocaine,OpioidsandMarijuana
SectionI:IntroductiontotheBrain
SectionII:IntroductiontotheRewardSystem
SectionIII:IntroductiontoDrugsofAbuse:Cocaine,Opiates(Heroin)andMarijuana(THC)
BackgroundInformationforthePresenter
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SectionI:IntroductiontotheBrain
1:Introduction
Introducethetopicofyourtalk.Indicatethatyouwillexplainhowthebrainbasicallyworksandhowdrugssuchascocaine,opiatesandmarijuanainteractwiththebrain'snormalactivities.Tellstudentsthatyouwillintroducetheconceptof"reward"whichisthepropertythatischaracteristicofmanyaddictivedrugs.Describethebrainasafunctionalunit;itismadeupofbillionsofnervecells(neurons)thatcommunicatewitheachotherusingelectricalandchemicalsignals.
2:Brainregionsandneuronalpathways
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Certainpartsofthebraingovernspecificfunctions.Pointtosensory,motor,associationandvisualcortextohighlightspecificfunctions.Pointtothehippocampustohighlighttheregionthatiscriticalformemory,forexample.Indicatethatnervecellsorneuronstravelfromoneareatoanotherviapathwaystosendandintegrateinformation.Show,forexample,therewardpathway.Startattheventraltegmentalarea(VTA)(inblue),followtheneuronalpathtothenucleusaccumbens(purple),andthenontothefrontalcortex.Explainthatthispathwaygetsactivatedwhenapersonreceivespositivereinforcementforcertainbehaviors("reward").Indicatethatyouwillexplainhowthishappenswhenapersontakesanaddictivedrug.
3:Neuronalstructure
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Remindthestudentthatpathwaysaremadeupofneurons.Describetheanatomyofaneuron(soma,dendrites,andaxonaremarkedwithtext).Statethatthisneuronisreal-asviewedthroughamicroscope.Explainthenormaldirectionofimpulseflow.Dendritesandsomareceivechemicalinformationfromneighboringneuronalaxons.Thechemicalinformationisconvertedtoelectricalcurrentswhichtraveltowardandconvergeonthesoma.Amajorimpulseisproduced(theactionpotential)andtravelsdowntheaxontowardtheterminal.Pointtotheterminal.
4:Thesynapseandsynapticneurotransmission
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Describethesynapseandtheprocessofchemicalneurotransmission.Indicatehowvesiclescontaininganeurotransmitter,suchasdopamine(thestars),movetowardthepresynapticmembraneasanelectricalimpulsearrivesattheterminal.Describetheprocessofdopaminerelease(showhowthevesiclesfusewiththepresynapticmembrane).Onceinsidethesynapticcleft,thedopaminecanbindtospecificproteinscalleddopaminereceptors(inblue)onthemembraneofaneighboringneuron.Introducetheideathatoccupationofreceptorsbyneurotransmitterscausesvariousactionsinthecell;activationorinhibitionofenzymes,entryorexitofcertainions.Statethatyouwilldescribehowthishappensinafewmoments.
5:Dopamineneurotransmission
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Usingtheclose-upofasynapse,continueusingdopamineforyourexampleofsynapticfunction.Explainthatitissynthesizedinthenerveterminalandpackagedinvesicles.Reiteratethestepsinneurotransmission.Showhowthevesiclefuseswiththemembraneandreleasesdopamine.Thedopaminemoleculescanthenbindtoadopaminereceptor(inblue).Afterthedopaminebinds,itcomesoffthereceptorandisremovedfromthesynapticcleftbyuptakepumps(alsoproteins)(inred)thatresideontheterminal.Thisprocessisimportantsothatnottoomuchdopamineisleftinthesynapticcleftatanyonetime.Alsopointoutthatthereisaneighboringneuron,whichreleasesanothercompoundcalledaneuromodulator.Inthiscaseitisan"endorphin"(blueflyingsaucers).Endorphinsbindtoopiatereceptors(ingreen)whichresideonthepost-synapticcellorinsomecasesontheterminalsofotherneurons(thisisnotshownsoitmustbepointedout).Theendorphinsaredestroyedbyenzymesratherthanremovedbyuptakepumps.
6:DopamineandtheproductionofcyclicAMP
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Usingtheclose-upview,explainwhathappenswhendopaminebindstoitsreceptor.Whendopaminebindstoitsreceptor,anotherproteincalledaG-protein(inpink)movesupclosetothedopaminereceptor.TheG-proteinsignalsanenzymetoproducecyclicadenosinemonophosphate(cAMP)molecules(ingreen)insidethecell.[SometimesthesignalcandecreaseproductionofcAMP,dependingonthekindofdopaminereceptorandG-proteinpresent.]Pointtothedopaminereceptor-G-protein/adenylatecyclasecomplex,andshowhowcAMPisgeneratedwhendopaminebindstoitsreceptor.IndicatethatcAMP(pointtothecyclic-lookingstructures)controlsmanyimportantfunctionsinthecellincludingtheabilityofthecelltogenerateelectricalimpulses.
7:Summaryofneuronaltransmission
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Usetheexampleoftwoneuronsmakingcontacttosummarizeneuronaltransmission.Pointtothecellonthetopandindicatethatelectricalimpulsesflowinthedirectiontowardtheterminal.Remindthestudentswhathappenswhenimpulsesreachtheterminal;neurotransmittersarereleased,theybindtotheirreceptors,andnewimpulsesaregeneratedinthecellonthebottom.Explainthatthisishowinformationtravelsfromneurontoneuron.
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SectionII:IntroductiontotheRewardSystem
1:Reward:drugself-administration
Introducetheconceptofpositivereinforcementorreward.Explainthatratswillpressalevertoself-administeraninjectionofcocaineorherointhatisinsertedintoeithertheperipheralbloodstream(leftimage)orintospecificbrainregions(rightimage).Theratkeepspressingtogetmorecocaineorheroinbecausethedrugsmaketheratfeelsogood.Thisiscalledpositivereinforcement,orreward.Naturalrewardsincludefood,water,andsex-eachisrequiredtomaintainsurvivalofourspecies.Animalsandpeoplewillcontinuetoexhibitabehaviorthatisrewarding,andtheywillceasethatbehaviorwhentherewardisnolongerpresent.Explainthatthereisactuallyapartofthebrainthatisactivatedbynaturalrewardsandbyartificialrewardssuchasaddictivedrugs.Thispartofthebrainiscalledtherewardsystem.Neuroscientistshavebeenabletopinpointtheexactpartsofthebraininvolved,withthehelpoftherats.Pointto
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thecartoonontherightandexplainthatratswillalsoself-administeraddictivedrugsdirectlyintotheirbrains,butonlyintoaspecificareaoftherewardsystem.Iftheinjectionneedleismovedlessthanamillimeterawayfromthiscrucialarea,theratwon'tpresstheleverformoredrug.Sobasedoninformationfromworkingwiththerats,scientistshavedrawnamapofthebrain,andlocatedthestructuresandpathwaysthatareactivatedwhenanaddictivedrugistakenvoluntarily.Tellthestudentsthatyouwillshowthemthis"map."
2:Therewardpathway
Tellstudentsthatthisisaviewofthebraincutdownthemiddle.Animportantpartoftherewardsystemisshownandthemajorstructuresarehighlighted:theventraltegmentalarea(VTA),thenucleusaccumbens(nuc.acc.)andtheprefrontalcortex.Also,thepathwayconnectingthesestructuresishighlighted.TheinformationtravelsfromtheVTAtothenucleusaccumbensandthenuptotheprefrontalcortex.Reiteratethatthispathwayisactivatedbyarewardingstimulus.[Notetoscientists-thisisnottheonlypathwayactivatedbyreward,otherstructuresareinvolvedtoo,butonlythispartofthepathwayisshownforsimplicity.]
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3:Injectionofcocaineintothenucleusaccumbens
Demonstratehowscientistslocatedthestructuresimportantfortheaddictivenatureofdrugs.Showthataratwillself-administercocainedirectlyintothenucleusaccumbens(ortheVTA)toactivatethepathway.PointtoanareaclosetothenucleusaccumbensorVTAandstatethatiftheinjectionisplacedinthisotherarea,theratwillnotpressthelevertoreceivethedrug.Indicatethatscientistsknowalotmorethanwherethedrugactstoproducerewardingeffects-theyalsoknowhowthedrugswork.Showexampleswithcocaine,heroin,andmarijuana.
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SectionIII:IntroductiontoDrugsofAbuse:Cocaine,Opiates(Heroin)andMarijuana(THC)
1:Localizationofcocaine"bindingsites"
Whenapersonsmokesorsnortscocaine,ittravelsquicklytothebrain.Althoughitreachesallareasofthebrain,itconcentratesinsomespecificareas.Thesearehighlightedwiththeturquoisesprinkles;theVTA,thenucleusaccumbens,andthecaudatenucleus(lighterturquoisesincethecaudateisinsidethehemisphere).Pointoutthatcocaineconcentratesespeciallyintherewardareasthatyouhavejustdiscussed.Cocaineaccumulationinotherareassuchasthecaudatenucleuscanexplainothereffectssuchasincreasedstereotypicbehaviors(pacing,nail-biting,scratching,etc..)
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2:Dopaminebindingtoreceptorsanduptakepumpsinthenucleusaccumbens
Explainthatcocaineconcentratesinareasofthebrainthatarerichindopaminesynapses.Reviewdopaminetransmissioninthenucleusaccumbens.Pointtodopamineinthesynapseandtodopamineboundtodopaminereceptorsandtouptakepumpsontheterminal.
3:Cocainebindingtouptakepumps:inhibitionofdopamineuptake
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Now,showwhathappenswhencocaineispresentinthesynapse.Cocaine(turquoise)bindstotheuptakepumpsandpreventsthemfromremovingdopaminefromthesynapse.Thisresultsinmoredopamineinthesynapse,andmoredopaminereceptorsareactivated.
4:IncreasedcAMPproducedinpost-synapticcell
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Inacloserview,showhowthisaffectsthefunctionofthecell.TheincreasedactivationofdopaminereceptorscausesincreasedproductionofcAMPinsidethepost-synapticcell.Thiscausesmanychangesinsidethecellthatleadtoabnormalfiringpatterns.
5:Summary:cocainebindinginnucleusaccumbensandactivationofrewardpathway
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Showthe"bigpicture,"Asaresultofcocaine'sactionsinthenucleusaccumbens(pointtothesprinklesofcocaineinthenuc.acc.),thereareincreasedimpulsesleavingthenucleusaccumbenstoactivatetherewardsystem.Indicatethatwithcontinueduseofcocaine,thebodyreliesonthisdrugtomaintainrewardingfeelings.Thepersonisnolongerabletofeelthepositivereinforcementorpleasurablefeelingsofnaturalrewards(food,water,sex).
6:Positronemissiontomography(PET)scanofapersononcocaine
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Cocainehasotheractionsinthebraininadditiontoactivatingreward.Scientistshavetheabilitytoseehowcocaineactuallyaffectsbrainfunctioninpeople.ThePETscanallowsonetoseehowthebrainusesglucose;glucoseprovidesenergytoeachneuronsoitcanperformwork.Thescansshowwherethecocaineinterfereswiththebrain'suseofglucose-oritsmetabolicactivity.Theleftscanistakenfromanormal,awakeperson.Theredcolorshowsthehighestlevelofglucoseutilization(yellowrepresentslessutilizationandblueshowstheleast).Therightscanistakenfromacocaineabuseroncocaine.Itshowsthatthebraincannotuseglucosenearlyaseffectively-showthelossofredcomparedtotheleftscan.Therearemanyareasofthebrainthathavereducedmetabolicactivity.Thecontinuedreductionintheneurons'abilitytouseglucose(energy)resultsindisruptionofmanybrainfunctions.
7:Localizationofopiatebindingsites
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Whenapersoninjectsheroinormorphine,ittootravelsquicklytothebrain.Pointtotheareaswhereopiatesconcentrate.TheVTA,nucleusaccumbens,caudatenucleusandthalamusarehighlighted.Theopiatesbindtoopiatereceptorsthatareconcentratedinareaswithintherewardsystem.Indicatethattheactionofopiatesinthethalamuscontributestotheirabilitytoproduceanalgesia.
8:Opiatesbindingtoopiatereceptorsinthenucleusaccumbens:increaseddopaminerelease
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Showhowopiatesactiviatetherewardsystemusingthenucleusaccumbensasanexample.Explainthattheactionisalittlemorecomplicatedthancocaine'sbecausemorethantwoneuronsareinvolved.Pointoutthatthreeneuronsparticipateinopiateaction:thedopamineterminal,anotherterminal(ontheright)containingadifferentneurotransmitter(probablyGABAforthosethatwouldliketoknow),andthepost-synapticcellcontainingdopaminereceptors.Showthatopiatesbindtoopiatereceptors(green)ontheneighboringterminalandthissendsasignaltothedopamineterminaltoreleasemoredopamine.[Incaseaninquisitivestudentaskshow,onetheoryisthatopiatereceptoractivationdecreasesGABArelease,whichnormallyinhibitsdopaminerelease,sodopaminereleaseisincreased.]
9:IncreasedcAMPproducedinpost-synapticcell
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Inacloserview,again,showhowthisaffectsthefunctionofthepost-synapticcell.Sincethereismoredopaminereleased,thereisincreasedactivationofdopaminereceptors,similartotheeffectofcocaine.ThiscausesincreasedproductionofcAMPinsidethepost-synapticcell,whichaltersthenormalactivityoftheneuron.
10:Summary:opiatebindinginnucleusaccumbensandactivationoftherewardpathway
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Showthe"bigpicture."Asaresultofopiateactionsinthenucleusaccumbens(pointtothesprinklesofopiatesinthenuc.acc.),thereareincreasedimpulsesleavingthenucleusaccumbenstoactivatetherewardsystem(pointtothefrontalcortex).Aswithcocaine,continueduseofopiatesmakesthebodyrelyonthepresenceofthedrugtomaintainrewardingfeelingsandothernormalbehaviors.Thepersonisnolongerabletofeelthebenefitsofnaturalrewards(food,water,sex)andcan'tfunctionnormallywithoutthedrugpresent.
11:LocalizationofTHCbindingsites
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Whenapersonsmokesmarijuana,theactiveingredient,cannabinoidsorTHC,travelsquicklytothebrain.PointtotheareaswhereTHC(magenta)concentrates.TheVTA,nucleusaccumbens,caudatenucleus,hippocampus,andcerebellumarehighlighted.THCbindstoTHCreceptorsthatareconcentratedinareaswithintherewardsystemaswellastheseotherareas.IndicatethattheactionofTHCinthehippocampusexplainsitsabilitytointerferewithmemoryandactionsinthecerebellumareresponsibleforitsabilitytocauseincoordinationandlossofbalance.
12:THCbindingtoTHCreceptorsinthenucleusaccumbens:increaseddopaminerelease
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[Notetoscientists-theinteractionofTHCwiththerewardsystemisnotfullyunderstoodatthispoint.Thefollowingdiscussionisbasedonrecentdata,butadditionaltheoriesmayemergeasweobtainmoredata.]StatethatscientistsknowtheleastaboutTHC.Overthelastfewyears,therehasbeenintensestudytodiscoverwhereandhowTHCworks.Onetheoryisthatitactsinasimilarwaytoopiates.Againusethenucleusaccumbensasanexample.Thesamethreeneuronsareprobablyinvolved:thedopamineterminal,anotherterminal(ontheright)containingadifferentneurotransmitter(probablyGABA),andthepost-synapticcellcontainingdopaminereceptors.AskthestudentsiftheycantellyouhowTHCmightwork.THCbindstoTHCreceptors(magenta)ontheneighboringterminalandthissendsasignaltothedopamineterminaltoreleasemoredopamine.[Again,itisprobablyapresynapticreceptoronGABAinterneuronsthatcontrolsdopaminerelease.]
13:IncreasedcAMPproducedinpost-synapticcell
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Inacloserview,showhowthisaffectsthefunctionofthepost-syanapticcell.Sincethereismoredopaminereleased,thereisincreasedactivationofdopaminereceptors.ThiscausesincreasedproductionofcAMPinsidethepost-synapticcellwhichaltersthenormalactivityoftheneuron.
14:Summary:THCbindinginnucleusaccumbensandactivationoftherewardpathway
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Showthe"bigpicture."AsaresultofTHCactionsinthenucleusaccumbens(pointtotheconcentrationofTHCinthenuc.acc.),thereareincreasedimpulsesleavingthenucleusaccumbenstoactivatetherewardsystem(pointtothefrontalcortex).Scientistsstilldon'tknowhowthecontinueduseofmarijuanaalterstherewardsystem.Indicatethatthisisanareaofintenseresearchbyneuroscientists.
15:Overallsummary:thesedrugsofabuseallactivatetherewardsystemviaincreasingdopamineneurotransmission
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Inthislastimage,thebindingofallthreedrugsisshowninoneoftherewardareas,thenucleusaccumbens.Summarizethateachdrugincreasestheactivityoftherewardpathwaybyincreasingdopaminetransmission.Thishappenseventhoughthedrugsactbydifferentmechanisms.Becauseofthewayourbrainsaredesigned,andbecausethesedrugsactivateaparticularbrainpathwayforreward,theyhavetheabilitytobeabused.Startadiscussion;askthestudentsiftheycanthinkofanyotherdrugsthatareabusedthatprobablyactivatetherewardsysteminthesameway.Answer:alcohol,nicotine,andamphetaminearegoodexamples.
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BackgroundInformationforthePresenter
Objectives
Theobjectiveoftheteachingpacketistoinformstudents(highschool)how3drugsofabuse(cocaine,opiates,marijuana)actuallyworkinthebrain.Thepacketisarrangedin3sections.Thefirstsectionintroducesthebrainandpresentssomebasicneurobiology,thesecondintroducestherewardpathwayandthethirdpresentsthemechanismofactionofeachdrugandhoweachaffectstherewardsystem.
BeforeEnteringtheClassroom
Arrangetotalkwiththeteacher(bytelephoneorinperson).
Obtaininformationontheagegroupandextentofbiologybackground.
Discussthesubjectsthatyouwillpresenttotheclass.
Ifpossible,meetwiththeteacher&reviewthepresentation;provideteacherwithsomebackgroundmaterialifrequested.
Solicitadvicefromtheteacheraboutteachingstrategies(e.g.whattodoifsomestudentsaredisruptiveornotlistening).
Readthenarrativescriptandpracticethepresentation-thisisdifferentfromascientificseminartopeers!
OnceintheClassroom
Introduceyourselftotheclass.
Talkbrieflyaboutyourpathtoyourcurrentjob.
Describewhatyoudo(simply).
Indicatetheobjectofyourpresentation.
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Invitequestionsduringyourpresentation.
Iftheopportunityarises,askquestionsofthestudents.
Bepreparedtodefineanywordsyouuse.
GeneralInstructions
Thepresentationshouldtakeapproximately30-40minutes(withoutquestions);itcanbepresentedin2classsessionsifsodesired.
Usethenarrativetextasaguide,itneednotberepeatedword-for-word.