Behavioral Neuroscience of Drug Addiction

390 Pages·2010·3.24 MB·English

by  Garret D. Stuber

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
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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
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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