The Neuropharmacology of Alcohol PDF
Preview The Neuropharmacology of Alcohol
Handbook of Experimental Pharmacology 248 Kathleen A. Grant · David M. Lovinger Editors The Neuropharmacology of Alcohol Handbook of Experimental Pharmacology Volume 248 Editor-in-Chief J.E.Barrett,Philadelphia EditorialBoard V.Flockerzi,Homburg M.A.Frohman,StonyBrook P.Geppetti,Florence F.B.Hofmann,Mu¨nchen M.C.Michel,Mainz C.P.Page,London W.Rosenthal,Jena K.Wang,Qingdao Moreinformationaboutthisseriesathttp://www.springer.com/series/164 Kathleen A. Grant (cid:129) David M. Lovinger Editors The Neuropharmacology of Alcohol Editors KathleenA.Grant DavidM.Lovinger DepartmentofBehavioralNeuroscience LaboratoryforIntegrativeNeuroscience OregonHealth&ScienceUniversity NationalInstitutesofHealth Portland,Oregon Bethesda,Maryland USA USA ISSN0171-2004 ISSN1865-0325 (electronic) HandbookofExperimentalPharmacology ISBN978-3-319-96522-2 ISBN978-3-319-96523-9 (eBook) https://doi.org/10.1007/978-3-319-96523-9 LibraryofCongressControlNumber:2018952524 This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protectionmayapply2018 All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionorinformationstorageand retrieval,electronicadaptation,computersoftware,orbysimilarordissimilarmethodologynowknown orhereafterdeveloped. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. Thepublisher,theauthorsandtheeditorsaresafetoassumethattheadviceandinformationinthisbook arebelievedtobetrueandaccurateatthedateofpublication.Neitherthepublishernortheauthorsorthe editorsgiveawarranty,expressedorimplied,withrespecttothematerialcontainedhereinorforany errorsoromissionsthatmayhavebeenmade.Thepublisherremainsneutralwithregardtojurisdictional claimsinpublishedmapsandinstitutionalaffiliations. ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG. Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Preface ThisvolumeoftheHandbookofExperimentalPharmacology,“TheNeuropharma- cology of Alcohol,” was an exciting and challenging editorial effort. Our under- standingofthepharmacologyofthesimpleorganiccompoundethanol(referredto asalcoholinthisvolume)hasflourishedinthepast40years.Thisvolumefocuses on the alcohol’s central nervous system (CNS) effects and its behavioral pharma- cologyrelatedtoabusepotential.Manyofalcohol’sinitialactionsonbraintargets thatwereidentifiedinthelate1980sandearly1990shavestoodthetestoftimeand technologicaldevelopments;however,farmoredepthandbreadthhasbeenadded toourunderstandingofalcohol’spharmacologyinthepasttwodecades.Withthis realityinmind,itwasdifficulttoassemble20ofthemostimportanttopicsforthis volume.Thereareregrettablegapsintheneurotransmittersystemscoveredandthe extent of phenotypic outcomes related to chronic alcohol exposure. Nevertheless, representativemechanismsofalcohol’sneuropharmacologyarepresented,wehope to the satisfaction of the interested reader. We have organized the volume by generalemphasisonneurotransmittersystems,neuropeptides,andionchannelsas wellasnewertopicsincludingneuroimmunesystems,genomicmechanisms,anda currentreviewofpreclinicalanimalandhumanclinicalstudiesofpharmacotherapy developments. The gamma-aminobutyric acid (GABA) and glutamatergic systems were argu- ablythefirstreceptorsystemsfoundtohavethesensitivityandselectivityexpected forreceptor-mediatedalcoholoutcomes.Theseaminoacidneurotransmitterscon- tinue to be the most studied in alcohol neuropharmacology. Furthermore, as the fieldcontinuestodefinebothpre-andpostsynapticmechanisms,neuroanatomical specificity and GABA–glutamate interactions are becoming prominent explanations of alcohol’s behavioral effects. Therefore, we highlight these recent developments with five chapters. A general overview of GABA -gated chloride A channelsasatargetofalcoholisprovidedbyChandler,Overton,Ruedi-Bettschen, and Platt. This is complemented by a chapter by Lovinger on presynaptic release mechanisms implicated in G-protein coupled receptor actions on GABAeric synapses. Notable is the range of brain areas where alcohol’s effects appear to alter synaptic efficacy and the potential cross talk with other drugs of abuse. The importance of alcohol’s interaction with neurosteroid GABA networks is A reviewed by Finn and Jimenez. The chapter by Cuzon Carlson emphasizes the v vi Preface striatumasabrainareawherealcoholalterstheexcitatoryandinhibitorybalanceof GABAergic and glutamatergic transmission. The contribution from Rossi and Richardson also emphasizes anatomical specificity, in this case recent data implicating the cerebellum as a site for alcohol’s abuse liability through effects on GABA channels. Next, the chapter by Hopf and Mangieri focuses on AMPA A glutamate receptor (AMPAR)-mediated effects of alcohol, where advances in selective antagonists have helped illuminate subunit-specific aspects of ethanol sensitivity. Finally, another ionotropic receptor system that is prominent in the abuse aspects of alcohol is the nicotinic acetylcholine receptors. The chapter by Klenowski and Tapper provides an excellent overview of separate and common targets of alcohol and nicotine, particularly in the mesolimbic pathways with an emphasisontheapparentsynergisticeffectsleadingtocomorbidaddiction. We selected two monoaminergic systems to highlight in this volume. The dopaminergic system has long occupied a predominant place in neuropharmacologicalaspectsofaddictivedrugs,includingalcohol.Inthereview bySiciliano,Karkhanis,Holleran,Melchior,andJones,dopaminergicmechanisms that are determined under similar experimental conditions and translate across speciesareemphasizedasawayofdisentanglingacomplexliterature.Inaddition to dopamine, the monoamine norepinephrine (NE) is also implicated in alcohol reinforcementmechanisms,particularlyinrelationtoarousal,emotionalregulation, andstressprocesses.ThereviewbyVazey,denHartog,andMoormanemphasizes recent findings and provides new directions for better understanding how the NE systemismaladaptivelyalteredbyalcohol. Theinteractionofalcoholandvoltage-dependentionchannelsisrepresentedby onereview oncalciumchannelsand two reviews on potassiumchannels.As with the GABA and glutamate systems, alcohol research has a relatively long history with voltage-sensitive calcium channels, particularly with neurophysiological disturbances such as tremors and seizures. The review by N’Gouemo takes this complexsubjectandemphasizestheroleofneuronalhomeostasisanditsdisruption by chronic alcohol exposure. The large conductance voltage- and calcium-depen- dentpotassiumchannel(BK)andchannelinteractionswithalcoholarereviewedby Dopico,Bukiya,andBettinger,withanemphasisonadaptationsunderlyingtoler- ance to alcohol. Comparatively new to the neuropharmacology of alcohol is disruptions in intrinsic neuronal excitability by alcohol-induced adaptations in small-conductance calcium-activated (SK), voltage-dependent, and G-protein- activated inwardly rectifying potassium channels. These potassium channel mechanismsrelatedtoalcoholandimpairedneuronalfiringarereviewedelegantly byCannady,Rinker,Nimitvilai,Woodward,andMulholland. The aspect of alcohol’s pharmacology that is receiving renewed attention is alcohol-induced neuroinflammation involving immune signaling molecules. For thissubject,wehaveincludedthreereviews.ThefirstreviewbyKim,McCullough, Poulson, Sanz-Garcia, Sheehan, Stravitsky, and Nagy provides the important per- spective of how alcohol interferes with the hepatic immune system. The second reviewbyColemanandCrewsfocusesoninnateimmunesignalsasmodulatorsof neurocircuitry involved in the addiction to alcohol and possibilities for new Preface vii treatmentapproaches.ThisisfollowedbyareviewfromRoberto,Patel,andBajo ontheeffectsofkeycytokinesonmolecularpropertiesandsynaptictransmission, particularly in the extended amygdala and hippocampus. From this collection of reviews,itisclearthattargetsandpharmacotherapiesthatemergefromthecancer biologyfieldcanberepurposedtoaddresswidespreadorgandysfunction,including neuroinflammation,associatedwithheavyalcoholdrinking. The final set of reviews on neuropharmacological mechanisms of alcohol includesareview bySchreiberandGilpinontheextended amygdalaandcortico- tropin-releasing factor as a basic allosteric mechanism propagating excessive drinking. This is followed by a review of alcohol’s interaction with dynorphin and orexin neuropeptide systems by Anderson, Moorman, and Becker. These two systems are closely interrelated and underlie homeostatic mechanisms that likely become dysfunctional under chronic alcohol exposure, leading to changes in motivationalstatesthatincreasefurtheralcoholconsumption.Thefinalmechanistic review is by Savarese and Lasek on genomic factors induced by alcohol that can change signal transduction mechanism and gene expression integral to long-term adaptations in chronic alcohol drinking. The emergence of new pharmacological agents that target transcriptional factors promises new directions in alcohol pharmacotherapy. We conclude this volume with highly informative, comprehensive, and timely reviews on the practical side of alcohol neuropharmacology: approaches and outcomes of preclinical and human clinical studies of alcohol pharmacotherapeutics. The review by Egli provides background on the role of animal models as sensitive and efficient for rapid screening, but emphasizes that better translational approaches are needed to have potential pharmacotherapies retain efficacy in the arena of human outpatient treatment. The final review, by Litten,Falk,Ryan,Fertig,andLeggio,providesahistoryandcurrentemphasison developingefficaciousandsafecompoundsfortreatingalcoholusedisorder. Wesincerelybelievethatthisvolumeprovidesavaluableandinstructiveview onthestateoftheartinourunderstandingofthedepthandbreadthofpast,present, andfutureneuropharmacologicalresearchonalcohol.Itremainsawonderthatthis simple 2-carbon alcohol can result in such complex neuropharmacology. There is nodoubtthataswelearnmoreaboutreceptorsystems,theircircuitry,co-modula- tion, adaptive capacities, and underlying functions, we will learn more about the complex processes that result in alcohol use disorders. We hope you find this volumehelpfulindefiningimportantdirectionsofthisexcitingresearch. Portland,OR,USA KathleenA.Grant Bethesda,MD,USA DavidM.Lovinger Contents PartI NeurotransmitterSystems GABA ReceptorSubtypeMechanismsandtheAbuse-Related A EffectsofEthanol:GeneticandPharmacologicalEvidence. . . . . . . . . . 3 CassieM.Chandler,JohnS.Overton,DanielaRüedi-Bettschen, andDonnaM.Platt PresynapticEthanolActions:PotentialRolesinEthanolSeeking. . . . . 29 DavidM.Lovinger DynamicAdaptationinNeurosteroidNetworksinResponse toAlcohol. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 DeborahA.FinnandVanessaA.Jimenez GABAandGlutamateSynapticCoadaptationstoChronicEthanol intheStriatum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 VerginiaC.CuzonCarlson TheCerebellarGABA RSystemasaPotentialTarget A forTreatingAlcoholUseDisorder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 DavidJ.RossiandBenD.Richardson DoAlcohol-RelatedAMPA-TypeGlutamateReceptorAdaptations PromoteIntake?. .. . . . . .. . . . . . .. . . . . . .. . . . . .. . . . . . .. . . . . . .. 157 F.WoodwardHopfandReginaA.Mangieri Molecular,Neuronal,andBehavioralEffectsofEthanolandNicotine Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 PaulM.KlenowskiandAndrewR.Tapper Cross-SpeciesAlterationsinSynapticDopamineRegulation AfterChronicAlcoholExposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 CodyA.Siciliano,AnushreeN.Karkhanis,KatherineM.Holleran, JamesR.Melchior,andSaraR.Jones CentralNoradrenergicInteractionswithAlcoholandRegulation ofAlcohol-RelatedBehaviors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239 ElenaM.Vazey,CarolinaR.denHartog,andDavidE.Moorman ix x Contents PartII IonChannels Voltage-SensitiveCalciumChannelsintheBrain:Relevance toAlcoholIntoxicationandWithdrawal. . . . . . . . . . . . . . . . . . . . . . . . 263 ProsperN’Gouemo Voltage-SensitivePotassiumChannelsoftheBKType andTheirCodingGenesAreAlcoholTargetsinNeurons. . . . . . . . . . . 281 AlexM.Dopico,AnnaN.Bukiya,andJillC.Bettinger ChronicAlcohol,IntrinsicExcitability,andPotassiumChannels: NeuroadaptationsandDrinkingBehavior. . . . . . . . . . . . . . . . . . . . . . . 311 ReginaldCannady,JenniferA.Rinker,SudaratNimitvilai, JohnJ.Woodward,andPatrickJ.Mulholland PartIII NeuroimmuneSystem HepaticImmuneSystem:AdaptationstoAlcohol. . . . . . . . . . . . . . . . . 347 AdamKim,RebeccaL.McCullough,KyleL.Poulsen,CarlosSanz-Garcia, MeganSheehan,AbramB.Stavitsky,andLauraE.Nagy InnateImmuneSignalingandAlcoholUseDisorders. . . . . . . . . . . . . . 369 LeonG.Coleman,Jr.andFultonT.Crews EthanolandCytokinesintheCentralNervousSystem. . . . . . . . . . . . . 397 MarisaRoberto,ReeshaR.Patel,andMichalBajo PartIV NeuropeptidesandGenomics Corticotropin-ReleasingFactor(CRF)Neurocircuitry andNeuropharmacologyinAlcoholDrinking. . . . . . . . . . . . . . . . . . . . 435 AllysonL.SchreiberandNicholasW.Gilpin ContributionofDynorphinandOrexinNeuropeptideSystems totheMotivationalEffectsofAlcohol. . . . . . . . . . . . . . . . . . . . . . . . . . 473 RachelI.Anderson,DavidE.Moorman,andHowardC.Becker TranscriptionalRegulatorsasTargetsforAlcohol Pharmacotherapies. . . .. . . .. . . . .. . . .. . . . .. . . . .. . . .. . . . .. . . .. 505 AntoniaM.SavareseandAmyW.Lasek PartV Pharmacotherapy AdvancingPharmacotherapyDevelopmentfromPreclinicalAnimal Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537 MarkEgli AdvancesinPharmacotherapyDevelopment:HumanClinical Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 579 RayeZ.Litten,DanielE.Falk,MeganL.Ryan,JoanneFertig, andLorenzoLeggio
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