negative reinforcement theories of addiction...negative reinforcement theories of addiction •...
TRANSCRIPT
Negative Reinforcement Theories of Addiction
• Sub-TypesofNegativeReinforcementModels• Self-MedicationHypothesis
• Drugsareusedtoself-medicate,i.e.,relievesymptomsthatoccurindependentofdruguse(e.g.,pain,anxiety)
• PhysicalDependenceHypothesis• DistressSyndromeReductionTheories,withdrawalavoidance• Withthedevelopmentoftoleranceandphysicaldependencedruguseissustainedinordertoavoidtheunpleasantconsequencesassociatedwithwithdrawal
• peoplecontinuetotakedrugstoease“distresssyndrome”(physicaland/orpsychological)associatedwiththecessationofdruguse
• perhapsduetoadaptationsinbrainrewardsystems(compensatoryreboundidea),oropponentprocess
BrainDysregulationinAddiction(CNSactivity,mood,behavior)
Koob&LeMoal,NeurobiologyofAddiction,2006
Normal
Addicted
Problems
• Peopleandanimalsself-administerdrugsatdosesthataretoolowtoproducephysicaldependence
• Thereisahightendencytorelapseevenafteranextendedperiodofabstinence,longafterwithdrawal
Conclusion: physical dependence and withdrawal are neither necessary nor sufficient conditions for addiction
• •“Physicaldependenceiscurrentlyviewednotsomuchasadirectcauseofdrugdependencebutasoneofseveralfactorsthatcontributetoitsdevelopment”
• (J.H.Jaffe,inA.Gilmanetal.(eds.),ThePharmacologicalBasisofTherapeutics,1990)
• “Forratsandmonkeysphysicaldependenceisneitheranecessarynorsufficientconditionforopiatestoactasreinforcers”
• (C.Schuster,inG.Edwardsetal.(eds.),TheNatureofDrugDependence,1990)
• “Theroleofphysicaldependenceinaddictionissuggestedtovaryfromdrugtodrugandtobeofsecondaryimportanceintheunderstandingofcompulsivedrugself-administration
• (R.A.Wise&M.A.Bozarth,PsychologicalReview,1987)
• Toleranceandwithdrawalarestillwidelystudied– Ethanolinhalation– Withdrawal-inducedseizures– Antinociceptivetolerance(hot-platetest)
Positive reinforcement theory of addiction
• Drugtakingismaintainedbecausedrugsactaspositivereinforcers:• thusincreasetheprobabilityofprecedingbehavior(drug-taking)• positivereinforcementmodelsgenerallyequatepositivereinforcementwithpleasure• (“pleasure-seeking”model)
Positive reinforcement
• “Theonlyexistingpositivereinforcementviewofaddictionthatmightqualifyasanexplanatorytheoryidentifiespositivereinforcementwithdrugeuphoria”.• Primarymotivationalforcedrivingdrugseekinganddrug-takingbehaviorintheaddictisthedesiretoobtainpleasure
(R.A.Wise&M.A.Bozarth,PsychologicalReview,1987,94:469)
Problems: “euphoria” models
• “...itwassupposedthatthepredictionofaddictionliabilitywasessentiallyequivalenttopredictionofeuphorigenicpower.Aswithmostself-evidentideas,themerematteroftherebeingessentiallynoevidenceinfavorofit,andmuchagainstit,hadlittleeffectonitsacceptance.”(Dews,1977)
Problems: “euphoria” models
• Theincentivevalueofdrugsisdissociablefromtheirsubjectivepleasurableeffects• “Wanting”drugs(motivationtotakedrugs)isdissociablefromtheirsubjectivepleasurableeffects(“liking”drugs)
• Howcanweassestheabusepotentialofdifferentdrugs,andstudythemechanismsbywhichdrugsproducerewardingeffectsanddependence• Canexaminethestimuluspropertiesofdrug
• (“whatdoesitfeellike?”)• Canexaminethereinforcing/incentivepropertiesofdrugs
• (“willyouworkforit?”;”doyou‘want’it?”).• Withameasureofthesedrugeffects,wecanassesse.g.ifaparticularneurotransmitterisinvolvedindrugreward
People “want” drugs that they don’t “like”
NeuronVolume76,Issue32012470-485
KeyPoint:Dopaminemediates“wanting”or“drug-seeking”or“incentivemotivation”
Incentivetotakedrugincreasesduringaddiction
IncentiveSensitizationTheory:RobinsonandBerridge,(1993)
Drug-induceddopamineincreasesasafunctionofwithdrawal
i.e.,opioidreceptorsmediatepleasure,butdopaminemediatestheincentive/addictiveproperties
dopamine
opioids
Incentivemotivation“wanting”
Subjectivepleasure“liking”
Drugs
Phases of SA
Incubation of craving during drug self-administration
• Twogroups:• Shortaccess(1hour/day)• Longaccess(6hours/day)
Withdrawal-induced escalation apparent in LgA rats.
Face validity to the extreme: addicted rats
• Ratsself-administeredintravenouscocaineforthreemonths• TheDSMcriteriaevaluated:
• Thesubjecthasdifficultystoppingdruguseorlimitingdrugintake• Thesubjecthasanextremelyhighmotivationtotakethedrug,withactivitiesfocusedonitsprocurementandconsumption
• Substanceuseiscontinueddespiteitsharmfulconsequences.
• (AtoD)Addiction-likebehaviorsinratspositiveforthepresenceofzero,one,two,orthreeaddiction-likecriteria.
• Anindividualwasconsideredpositiveforanaddiction-likecriterionwhenitsscoreforoneofthethreeaddiction-likebehaviorswasinthe66thto99thpercentileofthedistribution.• (A)Persistenceindrugseeking,asmeasuredbynumberofnose-pokesinthe
cocaine-associateddeviceduringtheno-drugperiodofthe54thSAsession.• (B)Resistancetopunishment,asmeasuredbychangeinthenumberofcocaine
self-infusions(expressedaspercentageofbaselineSA)whencocainedeliverywasassociatedwithanelectricshockbetweenthe72ndand74thSAsessions.
• (C)Motivationforthedrug,asmeasuredbythebreakingpointduringaprogressive-ratioscheduleperformedbetweenthe52ndand60thSAsessions.
• (D)Percentageofthetotalpopulation(n=58)ofratspositiveforzero,one,two,orthreeaddiction-likecriteria.
• ratsshowinghigh(blackcircles,HRein)orlow(opencircles,LRein)cocaine-inducedreinstatementafter30daysofwithdrawal
30days
• Developmentofaddiction-likebehaviorsoversubsequentcocaineSAsessionsinratsshowinghigh(blackcircles,HRein)orlow(opencircles,LRein)cocaine-inducedreinstatementafter5daysofwithdrawal.
• (A)Persistenceindrugseeking,asmeasuredbynumberofnose-pokesinthecocaine-associateddeviceduringtheno-drugperiod.
• (B)Resistancetopunishment,asmeasuredbychangeinthenumberofcocaineself-infusions(expressedaspercentageofbaselineSA)whencocainedeliverywasassociatedwithanelectricshock.
• (C)Motivationforthedrug,asmeasuredbythebreakingpointduringaprogressive-ratioschedule.
• (D)Drug-inducedreinstatement,asmeasuredbynumberofnose-pokesinthedrug-associateddeviceasafunctionoftheprimingdoseofcocaine.LReinandHReincontainedtherats(n=7pergroup)withthelowestandhighestreinstatement,respectively,inducedbycocaineinfusionat1.6mg/kg.