2025
Effects of Long-Term Cocaine Self-Administration on Kappa Opioid Receptors in Socially Housed Cynomolgus Monkeys as Assessed with PET Imaging and Neuronally Derived Exosomes
Johnson B, Allen M, Nader S, Sai K, Kumar A, Su Y, Singh S, Li S, Huang Y, Deep G, Nader M. Effects of Long-Term Cocaine Self-Administration on Kappa Opioid Receptors in Socially Housed Cynomolgus Monkeys as Assessed with PET Imaging and Neuronally Derived Exosomes. Biological Psychiatry 2025 PMID: 40054763, DOI: 10.1016/j.biopsych.2025.02.900.Peer-Reviewed Original ResearchLong-term cocaine self-administrationKappa-opioid receptorsCocaine self-administrationSelf-administrationKappa opioid receptor availabilityPeripheral measuresSocially housed monkeysOpioid receptorsCocaine intakeCocaine SAIntravenous cocaineCocaine misuseBrain regionsCocainePET imagingCynomolgus monkeysSocial rankPET studiesPharmacological interventionsMonkeysPET scansBrainBlood samplesDominant femalesSocial
2024
Compartmentalized pooling generates orientation selectivity in wide-field amacrine cells
Lei W, Clark D, Demb J. Compartmentalized pooling generates orientation selectivity in wide-field amacrine cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2411130121. PMID: 39602271, PMCID: PMC11626119, DOI: 10.1073/pnas.2411130121.Peer-Reviewed Original ResearchConceptsOrientation selectivityBand-pass spatial frequency tuningVisual systemReceptive fieldsSpatial frequency tuningWide-field amacrine cellsReceptive field modelOrientation detectionKappa-opioid receptorsAmacrine cellsDetecting orientationVisual sceneFrequency tuningGlycinergic inhibitionOpioid receptorsField modelSpecific membrane resistanceExcitatory inputSynaptic inputsCalcium imagingMouse retinaCalcium signalingDendritic compartmentsMicrocircuit levelPolarizationPotential Role for Buprenorphine in the Management of Comorbid Depression Among People with Chronic Pain and Long-Term Opioid Therapy Dependence
Manhapra A, Rosenheck R, Becker W. Potential Role for Buprenorphine in the Management of Comorbid Depression Among People with Chronic Pain and Long-Term Opioid Therapy Dependence. 2024, 148-164. DOI: 10.1093/9780197675250.003.0009.Peer-Reviewed Original ResearchLong-term opioid therapyKappa-opioid receptorsChronic painOpioid receptorsKappa-opioid receptor antagonismManagement of comorbid depressionTherapeutic agentsMOR agonismOpioid therapyOpioid taperAntidepressant effectsWorsening painOpioid dependenceSafety profileAgonist actionPoor outcomeClinical trialsAssociated with worsening depressionPainEtiological driversBuprenorphineReceptor affinityComorbid depressionOpioidReceptorsPreclinical and clinical efficacy of kappa opioid receptor antagonists for depression: A systematic review
Wong S, Le G, Vasudeva S, Teopiz K, Phan L, Meshkat S, Kwan A, Rhee T, Ho R, Choi H, Cao B, Rosenblat J, McIntyre R. Preclinical and clinical efficacy of kappa opioid receptor antagonists for depression: A systematic review. Journal Of Affective Disorders 2024, 362: 816-827. PMID: 39019223, DOI: 10.1016/j.jad.2024.07.030.Peer-Reviewed Original ResearchMajor depressive disorderKappa-opioid receptorsKappa-opioid receptor antagonistConventional antidepressantsOpioid receptor antagonistReceptor antagonistMeasures of anhedoniaClinical trialsPhase 3 pivotal trialsEarly stages of clinical trialsMu-opioid receptorsPhase 3 studyClinically-relevant dosesStages of clinical trialsDepressive disorderSystematic reviewDepressive symptomsMu-opioidOpioid receptorsAntidepressantsAdjunctive therapyClinical efficacyAdverse eventsAticaprantResearch vistasPET Imaging of Kappa Opioid Receptors in Socially Housed Female and Male Monkeys: Effects of Chronic Cocaine Self-Administration
Johnson B, Nader S, Sai K, Li S, Huang Y, Nader M. PET Imaging of Kappa Opioid Receptors in Socially Housed Female and Male Monkeys: Effects of Chronic Cocaine Self-Administration. Drug And Alcohol Dependence 2024, 260: 109961. DOI: 10.1016/j.drugalcdep.2023.109961.Peer-Reviewed Original ResearchCocaine use disorderKappa-opioid receptorsCocaine self-administrationCocaine-induced changesCocaine SASelf-administrationBinding potentialPositron emission tomographySocial rank differencesChronic cocaine self-administrationSocial rankDrug-naive monkeysKappa-opioid receptor antagonistKappa-opioid receptor agonistFDA-approved pharmacotherapiesOpioid receptorsRegulation of stressPositron emission tomography imagingCocaine intakeDynorphin/KOR systemKOR systemFood pelletsUse disorderExperiment 1Brain regionsA review of the kappa opioid receptor system in opioid use
Cayir S, Zhornitsky S, Barzegary A, Sotomayor-Carreño E, Sarfo-Ansah W, Funaro M, Matuskey D, Angarita G. A review of the kappa opioid receptor system in opioid use. Neuroscience & Biobehavioral Reviews 2024, 162: 105713. PMID: 38733895, DOI: 10.1016/j.neubiorev.2024.105713.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsKappa opioid receptor systemKappa-opioid receptorsOUD subjectsKappa-opioid receptor expressionOpioid withdrawal symptomsWithdrawal symptomsDynorphin levelsPeripheral blood lymphocytesOpioid useDrug-seeking/taking behaviorAnti-reward systemsKappa-opioid receptor antagonistClinical studiesCerebrospinal fluidOpioid receptor systemKOR/dynorphin systemDisorder subjectsOpioid receptorsOpioid intoxicationBlood lymphocytesReceptor systemOpioidWeb of ScienceClinical roleDynorphin
2022
Kappa opioid receptor antagonism protects working memory performance from mild stress exposure in Rhesus macaques
Wallace T, Martin W, Arnsten A. Kappa opioid receptor antagonism protects working memory performance from mild stress exposure in Rhesus macaques. Neurobiology Of Stress 2022, 21: 100493. PMID: 36532373, PMCID: PMC9755019, DOI: 10.1016/j.ynstr.2022.100493.Peer-Reviewed Original ResearchKappa-opioid receptorsKOR systemKappa opioid receptor antagonismNeurobehavioral disordersStress exposureSelective KOR antagonistOpioid receptor antagonismClinical evidence pointsBenzodiazepine inverse agonistStress-induced dysfunctionMild stress exposureKOR antagonistsReceptor antagonismMesocortical pathwayOpioid receptorsTherapeutic benefitKOR activityInverse agonistKOR expressionReceptor systemRhesus macaquesMild stress responseBrain networksEvidence pointsFunctional influenceDifferences in the association between kappa opioid receptors and pain among Black and White adults with alcohol use disorders
de Laat B, Nabulsi N, Huang Y, O'Malley SS, Morris ED, Krishnan‐Sarin S. Differences in the association between kappa opioid receptors and pain among Black and White adults with alcohol use disorders. Alcohol Clinical And Experimental Research 2022, 46: 1348-1357. PMID: 35633151, DOI: 10.1111/acer.14879.Peer-Reviewed Original ResearchConceptsCold pressor testAlcohol use disorderKappa-opioid receptorsPositron emission tomographyOpioid receptorsNaltrexone effectsUse disordersWhite participantsOpioid antagonist naltrexoneBlack participantsKOR involvementNaltrexone treatmentPain recoveryAntagonist naltrexoneOpioid systemNaltrexoneAlcohol cravingPainWhite adultsUnderlying biological basisEmission tomographyWhite individualsMore alcoholTreatmentPreliminary findingsNovel Pharmacological Agents for the Treatment of Cocaine Use Disorder
Hadizadeh H, Flores J, Nunes E, Mayerson T, Potenza M, Angarita G. Novel Pharmacological Agents for the Treatment of Cocaine Use Disorder. Current Behavioral Neuroscience Reports 2022, 9: 27-46. DOI: 10.1007/s40473-022-00246-z.Peer-Reviewed Original ResearchCocaine use disorderNovel pharmacological agentsUse disordersCocaine vaccinePharmacological agentsClinical supportNarrative reviewAlpha-adrenergic antagonistKappa-opioid receptorsCorticotropin-releasing factorCentral nervous systemPurpose of reviewClinical evidenceGlutamatergic agentsSerotonergic agentsCholinergic agentsOrexin antagonistsNeurobiological targetsDopamine pathwayArousal pathwayNervous systemExtension studyPromising agentCapacity of cocaineDisorders
2021
Social Rank, Behavioral Phenotypes and Kappa Opioid Receptor: PET Imaging Studies of Socially Housed Female and Male Monkey Models of Cocaine Use Disorder
Johnson B, Sai K, Nader S, Li S, Huang Y, Nader M. Social Rank, Behavioral Phenotypes and Kappa Opioid Receptor: PET Imaging Studies of Socially Housed Female and Male Monkey Models of Cocaine Use Disorder. The FASEB Journal 2021, 35 DOI: 10.1096/fasebj.2021.35.s1.03412.Peer-Reviewed Original ResearchKOR systemDynorphin/KOR systemBrain regionsCocaine reinforcementKappa opioid receptor systemPET imagingCocaine overdose deathsPositron emission tomography studyOpioid receptor systemKappa-opioid receptorsRecent positron emission tomography (PET) studyNonhuman primate modelEmission tomography studiesStress-induced relapseChronic social stressEffects of drugsCocaine use disorderPET imaging studiesBehavioral phenotypesAgonist tracersCocaine acquisitionSocial behaviorDynorphin levelsOpioid receptorsPrimate model
2019
The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving
de Laat B, Goldberg A, Shi J, Tetrault JM, Nabulsi N, Zheng MQ, Najafzadeh S, Gao H, Kapinos M, Ropchan J, O'Malley SS, Huang Y, Morris ED, Krishnan-Sarin S. The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving. Biological Psychiatry 2019, 86: 864-871. PMID: 31399255, DOI: 10.1016/j.biopsych.2019.05.021.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsAlcohol use disorderOpioid receptorsUse disordersNonselective opioid receptor antagonistModest clinical effectsEfficacy of naltrexoneOpioid receptor antagonistDSM-IV criteriaPositron emission tomographyAlcohol Urge QuestionnaireNaltrexone initiationNaltrexone therapyClinical effectsReceptor antagonistTherapeutic effectCingulate cortexDrinking paradigmHeavy drinkersBilateral insulaNaltrexoneAlcohol dependenceBrain regionsEmission tomographyPrefrontal cortexKappa-opioid receptors, dynorphin, and cocaine addiction: a positron emission tomography study
Martinez D, Slifstein M, Matuskey D, Nabulsi N, Zheng MQ, Lin SF, Ropchan J, Urban N, Grassetti A, Chang D, Salling M, Foltin R, Carson RE, Huang Y. Kappa-opioid receptors, dynorphin, and cocaine addiction: a positron emission tomography study. Neuropsychopharmacology 2019, 44: 1720-1727. PMID: 31026862, PMCID: PMC6785004, DOI: 10.1038/s41386-019-0398-4.Peer-Reviewed Original ResearchConceptsCocaine use disorderStress-induced relapsePositron emission tomographyCocaine bingeKappa-opioid receptor/dynorphin systemKOR selective agonistPositron emission tomography studyKappa-opioid receptorsCold pressor testCocaine self-administration sessionsEmission tomography studiesSelf-administration sessionsStress-induced cocaineEndogenous dynorphinDynorphin systemHealthy controlsPressor testSelective agonistPET scansAnimal studiesKOR bindingReceptor availabilitySignificant associationBrain regionsEmission tomographyMolecular and behavioral mechanisms mediating paclitaxel‐induced changes in affect‐like behavior in mice
Meade J, Toma W, Alkhlaif Y, Bagdas D, Obeng S, Selley D, Damaj M. Molecular and behavioral mechanisms mediating paclitaxel‐induced changes in affect‐like behavior in mice. The FASEB Journal 2019, 33: 807.1-807.1. DOI: 10.1096/fasebj.2019.33.1_supplement.807.1.Peer-Reviewed Original ResearchKappa-opioid receptorsPaclitaxel-induced changesDepression-like behaviorInjection of vehicleNucleus accumbensSucrose preferenceRole of KORSelective KOR antagonist norbinaltorphimineDopamine D 2 receptorsKOR antagonist norbinaltorphimineTreatment-resistant depressionFemale C57BL/6J miceQuality of lifeFull-text articlesBaby boomer populationCancer survivorsAntagonist norbinaltorphimineC57BL/6J miceOpioid receptorsCancer ageKOR agonistsNeurochemical targetsTherapeutic interventionsPalatable foodProdynorphin mRNASocial status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers
Matuskey D, Dias M, Naganawa M, Pittman B, Henry S, Li S, Gao H, Ropchan J, Nabulsi N, Carson RE, Huang Y. Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers. Neuropsychopharmacology 2019, 44: 1714-1719. PMID: 30928993, PMCID: PMC6785144, DOI: 10.1038/s41386-019-0379-7.Peer-Reviewed Original ResearchConceptsBody mass indexKappa-opioid receptorsPositron emission tomographyAgonist radiotracerKOR systemOpioid receptorsTime-activity curvesBarratt Simplified MeasureAnterior cingulate cortexArterial blood samplingMultilinear analysis-1 (MA1) methodPET imaging studiesKOR levelsMass indexPreclinical modelsFrontal cortexHealthy volunteersRegional time-activity curvesBlood samplingPET scansCingulate cortexImaging studiesEmission tomographyVentral striatumRegional volumesNovel Kappa Opioid Receptor Agonist as Improved PET Radiotracer: Development and in Vivo Evaluation
Li S, Zheng M, Naganawa M, Gao H, Pracitto R, Shirali A, Lin SF, Teng JK, Ropchan J, Huang Y. Novel Kappa Opioid Receptor Agonist as Improved PET Radiotracer: Development and in Vivo Evaluation. Molecular Pharmaceutics 2019, 16: 1523-1531. PMID: 30726092, DOI: 10.1021/acs.molpharmaceut.8b01209.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsAgonist radiotracerOpioid receptorsNovel kappa-opioid receptor agonistKappa-opioid receptor agonistFast tissue kineticsNonselective opioid receptorTissue kineticsOpioid receptor agonistsDose-dependent mannerMultilinear analysis-1 (MA1) methodHigh specific bindingSpecific bindingAgonist tracersHigh binding regionsReceptor agonistRegional time-activity curvesSpecific binding signalsTime-activity curvesArterial activityImproved imaging propertiesRhesus monkeysDrug abusePET radiotracersParent fraction
2018
PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age
Vijay A, Cavallo D, Goldberg A, de Laat B, Nabulsi N, Huang Y, Krishnan-Sarin S, Morris ED. PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age. Neuropsychopharmacology 2018, 43: 2539-2547. PMID: 30188515, PMCID: PMC6224533, DOI: 10.1038/s41386-018-0199-1.Peer-Reviewed Original ResearchConceptsHealthy control cohortVolume of distributionOpioid receptor systemKappa-opioid receptorsOpioid receptorsDelta opioid receptor systemReceptor systemMu-opioid receptor systemOpioid receptor availabilityPotential pharmacological targetEffect of ageAge-related declineControl cohortPET scansAntagonist tracersReceptor availabilityMultivariate analysisPharmacological targetsPET imagingReceptorsAgePartial volume correctionCohortVT valuesPresent studyKappa opioid receptor binding in major depression: A pilot study
Miller JM, Zanderigo F, Purushothaman PD, DeLorenzo C, Rubin‐Falcone H, Ogden RT, Keilp J, Oquendo MA, Nabulsi N, Huang YH, Parsey RV, Carson RE, Mann JJ. Kappa opioid receptor binding in major depression: A pilot study. Synapse 2018, 72: e22042. PMID: 29935119, PMCID: PMC7599086, DOI: 10.1002/syn.22042.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsMajor depressive disorderPositron emission tomographyHealthy volunteersRecent life stressKOR bindingLife stressKappa-opioid receptor bindingCurrent major depressive disorderPilot studyVoxel-wise contrastsWhole-brain voxel-wise analysisOpioid receptor bindingSubstance use disordersCo-occurring moodSalivary cortisol levelsVoxel-wise analysisTrier Social Stress TestCortisol areaRaphe nucleusOpioid receptorsPsychotic featuresDepressive disorderMajor depressionPathological response
2016
PET imaging reveals sex differences in kappa opioid receptor availability in humans, in vivo.
Vijay A, Wang S, Worhunsky P, Zheng MQ, Nabulsi N, Ropchan J, Krishnan-Sarin S, Huang Y, Morris ED. PET imaging reveals sex differences in kappa opioid receptor availability in humans, in vivo. American Journal Of Nuclear Medicine And Molecular Imaging 2016, 6: 205-14. PMID: 27648372, PMCID: PMC5004062.Peer-Reviewed Original ResearchKappa-opioid receptorsOpioid receptorsSex differencesOpioid receptor availabilityTreatment of painHealthy control menDelta-opioid receptorsVolume of distributionEfficacy of treatmentKappa opioid analgesicsMultiple brain regionsOpioid analgesicsKOR systemControl menAntagonist tracersPET scansReceptor availabilityVoxel levelPharmacological targetsBrain regionsPET imagingAddiction withdrawalReceptorsTreatmentPartial volume correction
2014
Kinetic Modeling of 11C-LY2795050, A Novel Antagonist Radiotracer for PET Imaging of the Kappa Opioid Receptor in Humans
Naganawa M, Zheng MQ, Nabulsi N, Tomasi G, Henry S, Lin SF, Ropchan J, Labaree D, Tauscher J, Neumeister A, Carson RE, Huang Y. Kinetic Modeling of 11C-LY2795050, A Novel Antagonist Radiotracer for PET Imaging of the Kappa Opioid Receptor in Humans. Cerebrovascular And Brain Metabolism Reviews 2014, 34: 1818-1825. PMID: 25182664, PMCID: PMC4269759, DOI: 10.1038/jcbfm.2014.150.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsMultilinear analysis 1Opioid receptorsNovel kappa opioid receptorDistribution volumePositron emission tomography (PET) imagingEmission Tomography ImagingLow intersubject variabilityTwo-tissue compartment modelAntagonist radiotracersOral naltrexoneNondisplaceable distribution volumeBaseline scanLY2795050Human studiesArterial input functionPET imagingTomography imagingIntersubject variabilityNaltrexoneEvaluation of the agonist PET radioligand [11C]GR103545 to image kappa opioid receptor in humans: Kinetic model selection, test–retest reproducibility and receptor occupancy by the antagonist PF-04455242
Naganawa M, Jacobsen LK, Zheng MQ, Lin SF, Banerjee A, Byon W, Weinzimmer D, Tomasi G, Nabulsi N, Grimwood S, Badura LL, Carson RE, McCarthy TJ, Huang Y. Evaluation of the agonist PET radioligand [11C]GR103545 to image kappa opioid receptor in humans: Kinetic model selection, test–retest reproducibility and receptor occupancy by the antagonist PF-04455242. NeuroImage 2014, 99: 69-79. PMID: 24844744, PMCID: PMC4140089, DOI: 10.1016/j.neuroimage.2014.05.033.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsTest-retest reproducibilityTest-retest variabilityAbsolute test-retest variabilityPF-04455242Time-activity curvesIntra-class coefficientOpioid receptorsRegional time-activity curvesMetabolite-corrected arterial input functionHuman positron emission tomography studiesPositron emission tomography studySelective KOR antagonistEmission tomography studiesReceptor occupancy studiesSuitable reference regionHalf maximal inhibitory concentrationAgonist tracersRegional VTAgonist PET radioligandOral doseKOR antagonistsMaximal inhibitory concentrationOral administrationPreclinical models
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