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 roleDynorphinThe endogenous opioid system in the medial prefrontal cortex mediates ketamine’s antidepressant-like actions
Jiang C, DiLeone R, Pittenger C, Duman R. The endogenous opioid system in the medial prefrontal cortex mediates ketamine’s antidepressant-like actions. Translational Psychiatry 2024, 14: 90. PMID: 38346984, PMCID: PMC10861497, DOI: 10.1038/s41398-024-02796-0.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAction of ketamineEndogenous opioid systemAntidepressant-like actionOpioid systemB-endorphinKetamine treatmentAntidepressant-like actions of ketamineBehavioral actions of ketamineAntidepressant actions of ketamineBehavioral effects of ketamineSingle dose of ketamineAntidepressant-like effectsLevels of B-endorphinAcute systemic administrationEffects of ketamineDose of ketamineOpioid receptor antagonistAntidepressant actionPrefrontal cortexActivation of opioid receptorsBehavioral effectsBehavioral actionsCompetitive opioid receptor antagonistOpioid receptors
2023
Comorbid alcohol use disorder and posttraumatic stress disorder: A proof‐of‐concept randomized placebo‐controlled trial of buprenorphine and naltrexone combination treatment
Davis L, Petrakis I, Pilkinton P, Nolen T, Vandergrift N, Hirsch S, Norrholm S, Kosten T. Comorbid alcohol use disorder and posttraumatic stress disorder: A proof‐of‐concept randomized placebo‐controlled trial of buprenorphine and naltrexone combination treatment. Alcohol Clinical And Experimental Research 2023, 47: 1756-1772. PMID: 37468230, DOI: 10.1111/acer.15155.Peer-Reviewed Original ResearchComorbid alcohol use disorderAlcohol use disorderPosttraumatic stress disorderPlacebo-controlled trialWorld Health OrganizationReceptor antagonismOpioid receptorsUse disordersExtended-release injectable naltrexoneKappa-opioid receptor antagonistStress disorderClinician-Administered PTSD ScalePrimary composite outcomeEffective pharmacologic treatmentOpioid receptor antagonistOpioid receptor antagonismMu-opioid receptorsCombination of buprenorphineBinary primary outcomeTimeline Follow-BackAUD outcomesBuprenorphine 2Injectable placeboPrimary timepointInjectable naltrexoneReview of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome
Walters A, Li Y, Koo B, Ondo W, Weinstock L, Champion D, Afrin L, Karroum E, Bagai K, Spruyt K. Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome. Brain 2023, 147: 26-38. PMID: 37633259, PMCID: PMC10796165, DOI: 10.1093/brain/awad283.Peer-Reviewed Original ResearchConceptsRestless legs syndromeMu-opioid receptorsRLS patientsEndogenous opioidsLegs syndromeOpioid receptorsSerum ironΒ-endorphinMelanocortin systemIdiopathic restless legs syndromeRLS-like symptomsPeriodic limb movementsLow serum ironWild-type miceSensory changesMelanocyte stimulating hormoneReceptor blockersSerum ferritinAutopsy studyStriatal dopamineAdrenocorticotropic hormoneStimulating hormoneDopaminergic systemMouse modelTherapeutic efficacyKetamine
Shergill S, Vadivelu N. Ketamine. 2023, 195-205. DOI: 10.1007/978-3-031-21291-8_13.Peer-Reviewed Original ResearchPost-operative pain controlPost-operative analgesiaSympathetic nervous systemMaintenance of anesthesiaMultiple surgical proceduresMu-opioid receptorsNMDA receptor antagonismComplete anestheticERAS protocolOperative analgesiaAnalgesic benefitPain controlPulmonary diseaseSeptic shockChronic painReceptor antagonismSubanesthetic dosesOpioid receptorsPotent analgesicSurgical proceduresHepatic enzymesNervous systemPartial agonistKetaminePatients
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 findings
2021
Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine
Shokri‐Kojori E, Naganawa M, Ramchandani VA, Wong DF, Wang G, Volkow ND. Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine. Human Brain Mapping 2021, 43: 1419-1430. PMID: 34873784, PMCID: PMC8837588, DOI: 10.1002/hbm.25733.Peer-Reviewed Original ResearchConceptsOpioid receptor availabilityStriatal DA releaseDA releaseOpioid receptorsReceptor availabilityDopamine releaseStriatal dopamine releaseOpioid use disorderBrain-wide distributionInverse associationHealthy controlsStriatal distributionClinical studiesStriatal patternUse disordersSubcortical regionsVentral striatumGray matter segmentsReceptorsNaloxoneMorphineStriatumDA targetsRelease patternReleaseSocial 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 cortexRigorous Trial Design Is Essential to Understand the Role of Opioid Receptors in Ketamine’s Antidepressant Effect—Reply
Krystal JH, Yoon G, Petrakis IL. Rigorous Trial Design Is Essential to Understand the Role of Opioid Receptors in Ketamine’s Antidepressant Effect—Reply. JAMA Psychiatry 2019, 76: 658-659. PMID: 31042270, DOI: 10.1001/jamapsychiatry.2019.0763.Peer-Reviewed Original ResearchMolecular 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
Pharmacological and Behavioral Treatment of Opioid Use Disorder
Sofuoglu M, DeVito E, Carroll K. Pharmacological and Behavioral Treatment of Opioid Use Disorder. Psychiatric Research And Clinical Practice 2018, 1: 4-15. PMCID: PMC9175946, DOI: 10.1176/appi.prcp.20180006.Peer-Reviewed Original ResearchOpioid use disorderMedication-assisted treatmentSubstance use conditionsBehavioral treatmentTreatment retentionUse disordersBehavioral interventionsOpioid withdrawal symptomsFirst-line treatmentMechanism of actionOUD treatmentComorbid conditionsMedication complianceWithdrawal symptomsClinical overviewClinical guidelinesOpioid receptorsAdrenergic agonistsNonsystematic reviewDrug AdministrationKey pharmacologicalBehavioral therapyTreatment effectivenessComplex needsTreatment
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