Behavioral Neuroscience of Drug Addiction PDF
Preview Behavioral Neuroscience of Drug Addiction
Current Topics in Behavioral Neurosciences Series Editors: Mark Geyer, La Jolla, CA, USA Bart Ellenbroek, Hamburg, Germany Charles Marsden, Nottingham, UK Aboutthisseries Current Topics in Behavioral Neurosciences provides critical and comprehensive discussions of the most significant areas of behavioral neuroscience research, written by leading international authorities. Each volume offers an informative andcontemporaryaccountofitssubject,makingitanunrivalledreferencesource. Titlesinthisseriesareavailableinbothprintandelectronicformats. With the development of new methodologies for brain imaging, genetic and genomicanalyses,molecularengineeringofmutantanimals,novelroutesfordrug delivery,andsophisticatedcross-speciesbehavioralassessments,itisnowpossible tostudybehaviorrelevanttopsychiatricandneurologicaldiseasesanddisorderson the physiological level.The Behavioral Neurosciences series focuses on ‘‘transla- tional medicine’’ and cutting-edge technologies. Preclinical and clinical trials for thedevelopment ofnewdiagnosticsandtherapeuticsaswellasprevention efforts arecoveredwheneverpossible. David W. Self Julie K. Staley l Editors Behavioral Neuroscience of Drug Addiction Editors Prof.Dr.DavidW.Self JulieK.Staley{,Ph.D. UniversityofTexas DepartmentofPsychiatry SouthwesternMedicalCenter YaleUniversity Dept.Psychiatry SchoolofMedicine 5323HarryHinesBlvd. VACHS116A2 DallasTX75390-9070 950CampellAve. USA WestHavenCT06516 [email protected] USA ISSN1866-3370 e-ISSN1866-3389 ISBN978-3-642-03000-0 e-ISBN978-3-642-03001-7 DOI10.1007/978-3-642-03001-7 SpringerHeidelbergDordrechtLondonNewYork LibraryofCongressControlNumber:2009938007 #Springer-VerlagBerlinHeidelberg2010 Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthematerialis concerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broadcasting, reproductiononmicrofilmorinanyotherway,andstorageindatabanks.Duplicationofthispublication orpartsthereofispermittedonlyundertheprovisionsoftheGermanCopyrightLawofSeptember9, 1965,initscurrentversion,andpermissionforusemustalwaysbeobtainedfromSpringer.Violationsare liabletoprosecutionundertheGermanCopyrightLaw. Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoesnotimply, evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevantprotectivelaws andregulationsandthereforefreeforgeneraluse. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and applicationcontained in thisbook.In everyindividualcasethe usermust checksuchinformationby consultingtherelevantliterature. Coverillustration:Artisticrepresentationofoscillatorysynchronyandtimingofneuronsinnetworksby GyorgyBuzsaki Coverdesign:WMXDesignGmbH,Heidelberg,Germany Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Drug addiction is a chronically relapsing mental illness involving severe motivationaldisturbancesandlossofbehavioralcontrolleadingtopersonaldevas- tation.Thedisorderafflictsmillionsofpeople,oftenco-occurringwithothermental illnesses with enormous social and economic costs to society. Several decades of research have established that drugs of abuse hijack the brain’s natural reward substrates, and that chronic drug use causes aberrant alterations in these reward- processing systems. Such aberrations may be demonstrated at the cellular, neuro- transmitter, and regional levels of information processing using either animal modelsorneuroimaginginhumansfollowingchronicdrugexposure.Behaviorally, these neural aberrations manifest as exaggerated, altered or dysfunctional expres- sion of learned behavioral responses related to the pursuit of drug rewards, or to environmental factors that precipitate craving and relapse during periods of drug withdrawal.Currentresearcheffortsareaimedatunderstandingtheassociativeand causalrelationshipsbetweentheseneurobiologicalandbehavioralevents,suchthat treatmentoptionswillultimatelyemploytherapeuticameliorationofneuraldeficits andrestorationofnormalbrainprocessingtopromoteeffortstoabstainfromfurther druguse. TheBehavioralNeuroscienceofDrugAddiction,partoftheSpringerserieson Current Topics in Behavioral Neurosciences, contains scholarly reviews by noted experts on multiple topics from both basic and clinical neuroscience fields. In the firsttwochapters,recenttechnologicaladvancesintheabilitytomonitorsynaptic neuroplasticity and transient dopamine release events are discussed in relation to drug and alcohol addiction models. These studies have greatly advanced our understandingofhowchronicdrugexposurechangestheresponsivenessofprimary reward substrates for drugs of abuse. Subsequent chapters illustrate how these events translate into addictive behavior and recruit additional brain regions involved in reward-related learning and behavioral disinhibition. Other chapters delveintotherelationshipbetweenheighteneddrugresponsivityandthepropensity for relapse, and the neurobiology of anhedonia after chronic drug use is discon- tinued. Together, these chapters provide a focused and critical review of current animal models and methods along with functional relationships between v vi Preface neurobiologicalandbehavioralchange.Manyoftheneurobiologicalandbehavior- al changes produced by chronic drug exposure in animals are reflected in human studies using modern neuroimaging and neurocognitive analyses, while others differ.Thesecondpartofthevolumeisdedicatedtostudiesinhumandrugabusers, beginning with two chapters on alterations in drug and neurotransmitter receptor levels, dopamine release, and their relationship to drug taking and craving. In addition,theassociationofgenomicmarkerswithvulnerabilitytodrugandalcohol addictionisreviewedinrelationtogenesknowntobeinvolvedintransmittingdrug signals and drug metabolism, and other approaches to identify novel genes asso- ciatedwithaddictedphenotypesthatcouldultimatelyserveastargetsfortreatment. Three chapters discuss the various cognitive abnormalities that accompany drug addiction,includingdeficitsinattention,memory,andexecutivecontrol,suscepti- bility of the adolescent brain, and the impact of such changes on the inability to makeappropriateandbeneficiallifechoicesinthecontextofabehavioraleconom- ic model of addiction. These latter chapters illustrate the global impact of drug- induced alterations discussed in earlier chapters on complex neurocircuitry involved in the intricate interplay between cognitive processing and decision- making.Finally,whileseveralnon-pharmacologicaltreatmentsforaddictionhave beenexplored,anexplosioninpotentialpharmacologicaltargetshasleadtoseveral novel treatments based on known and unknown mechanisms of action, and the latestfindingsarecomparedwithmoretraditionalapproaches. Thefindingsreviewedinthisvolumesuggestthatanemergingconsensusexists for the underlying pathology of drug addiction. Basic neuroscience research con- ducted in animal models suggests that neuroadaptations in limbic brain regions promote drug-taking behavior by enhancing the neural substrates of primary drug reward, while weakening neural mechanisms of inhibitory control. The latter is paralleled in humans by deficits in neocortical function and executive/cognitive information processing. However, human neuroimaging studies also suggest that drug addiction is associated with deficits in dopaminergic neurotransmission, the major neural substrate for primary drug reward. These and other discrepancies indicatethatmoreworkisneededtoreconcilethefindingsfromanimalmodelsand human drug addiction. Furthermore, there are numerous other drug-induced changes that encompass regulation of gene expression, intracellular signaling molecules, and several other neurotransmitter, metabolic and morphological changesthathavebeenidentified,buttheirrelevancetohumanbehavioralchange isunknown.Ultimately,itisimportantforanimalmodelstobetteremulatehuman cognitiveabnormalitiessothatcriticalcause-effectrelationshipsbetweenneurobi- ological and behavioral change may be determined. We hope the breadth of behavioralneuroscienceendeavorcontainedinthisvolumewillassistindirecting future research aimed at integrating human and animal work towards a cohesive bodyofresearchwithsubstantialimplicationsfortreatment. Dallas,TX DavidW.Self { WestHaven,CT JulieK.Staley Dedication Dr. Julie Staley passed away on July 25, 2009 shortly after completing her work as co-editor for this book. Her struggle with a long-term illness never once diminished her devotion and vigor for scientific endeavor, and herprofounddedicationtothisproject. ThisbookisdedicatedtoJulie,andthe tireless enthusiasm she displayed in liferemainsaninspirationforallofus. Dr.JulieStaley DavidSelf KellyCosgrove Contents PartI PreclinicalNeuroscience NeuroplasticAlterationsintheLimbicSystemFollowingCocaine orAlcoholExposure ............................................................ 3 GarretD.Stuber,F.WoodwardHopf,KayM.Tye,BillyT.Chen, andAntonelloBonci DopamineSignalingintheNucleusAccumbensofAnimals Self-AdministeringDrugsofAbuse ........................................... 29 IngoWilluhn,MatthewJ.Wanat,JeremyJ.Clark,andPaulE.M.Phillips AmygdalaMechanismsofPavlovianPsychostimulant ConditioningandRelapse ...................................................... 73 DeanneM.BuffalariandRonaldE.See PrefrontalCorticalRegulationofDrugSeekinginAnimal ModelsofDrugRelapse ...................................................... 101 HeatherC.Lasseter,XiaohuXie,DonnaR.Ramirez,andRitaA.Fuchs NeuralSubstratesofPsychostimulantWithdrawal-Induced Anhedonia ..................................................................... 119 ManoranjanS.D’SouzaandAthinaMarkou SensitizationProcessesinDrugAddiction .................................. 179 LoukJ.M.J.VanderschurenandR.ChristopherPierce PartII ClinicalNeuroscience ImagingReceptorChangesinHumanDrugAbusers ...................... 199 KellyP.Cosgrove ix x Contents ImagingNeurotransmitterReleasebyDrugsofAbuse .................... 219 DianaMartinezandRajeshNarendran ImagingCognitiveDeficitsinDrugAbuse .................................. 247 ThomasLundqvist NeuralMarkersofGeneticVulnerabilitytoDrugAddiction ............. 277 DanielJ.Mu¨ller,OlgaLikhodi,andAndreasHeinz TheRoleofExecutiveControlinHumanDrugAddiction ................ 301 RobertHester,DanI.Lubman,andMuratYu¨cel TheBehavioralEconomicsofDrugDependence:Towardsthe ConsilienceofEconomicsandBehavioralNeuroscience ................... 319 WarrenK.Bickel,RichardYi,E.TerryMueller,BryanA.Jones, andDarrenR.Christensen NovelPharmacologicalApproachestoDrugAbuseTreatment ........... 343 EllenEdens,AlfredoMassaandIsmenePetrakis Index ........................................................................... 387 Contributors WarrenK.Bickel Departments of Psychiatry and Radiology, Center for Addiction Research, University of Arkansas for Medical Sciences, 4301 W. Markham # 554, Little Rock,AR72205,USA,[email protected] AntonelloBonci Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858HortonStreet,Emeryville,CA94608,USA,[email protected] DeanneM.Buffalari DepartmentofNeuroscience,MedicalUniversityofSouthCarolina,BSB416173 AshleyAvenue,Charleston,SC29425,USA BillyT.Chen Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858HortonStreet,Emeryville,CA94608,USA AnnaRoseChildress Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia,PA19104,USA,[email protected] JeremyJ.Clark DepartmentofPsychiatryandBehavioralScience,UniversityofWashington,Box 356560,SeattleWA98195-6560,USA KellyCosgrove DepartmentsofPsychiatry,YaleUniversitySchoolofMedicine&VACHS116A6, 950CampbellAvenue,WestHaven,CT06516,USA,[email protected] xi
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