2022
Differences 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 findings
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 tomographySocial 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 volumes
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
2013
Synthesis and Evaluation of 11C-LY2795050 as a κ-Opioid Receptor Antagonist Radiotracer for PET Imaging
Zheng MQ, Nabulsi N, Kim SJ, Tomasi G, Lin SF, Mitch C, Quimby S, Barth V, Rash K, Masters J, Navarro A, Seest E, Morris ED, Carson RE, Huang Y. Synthesis and Evaluation of 11C-LY2795050 as a κ-Opioid Receptor Antagonist Radiotracer for PET Imaging. Journal Of Nuclear Medicine 2013, 54: 455-463. PMID: 23353688, PMCID: PMC3775344, DOI: 10.2967/jnumed.112.109512.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsAntagonist radiotracersSelective kappa opioid receptorPET imagingKOR knockout micePathophysiology of depressionSelective KOR antagonistRadioligand competition binding assaysEx vivo analysisDose-dependent mannerFavorable pharmacokinetic propertiesFull antagonist activityKOR antagonistsPeripheral metabolismKOR agonistsTracer candidatesLY2795050Sprague-DawleyAntagonist tracersKnockout miceSpecific binding signalsCompetition binding assaysRhesus monkeysPharmacokinetic propertiesAntagonist activity
2010
Synthesis and evaluation of [C-11]LY2795050, an antagonist PET imaging tracer for the kappa opioid receptors
Zheng M, Nabulsi N, Tomasi G, Mitch C, Quimby S, Barth V, Rash K, Masters J, Navarro A, Seest E, Carson R, Huang Y. Synthesis and evaluation of [C-11]LY2795050, an antagonist PET imaging tracer for the kappa opioid receptors. NeuroImage 2010, 52: s120. DOI: 10.1016/j.neuroimage.2010.04.098.Peer-Reviewed Original Research