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 femalesSocialOnce-Weekly Semaglutide in Adults With Alcohol Use Disorder
Hendershot C, Bremmer M, Paladino M, Kostantinis G, Gilmore T, Sullivan N, Tow A, Dermody S, Prince M, Jordan R, McKee S, Fletcher P, Claus E, Klein K. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder. JAMA Psychiatry 2025, 82 PMID: 39937469, PMCID: PMC11822619, DOI: 10.1001/jamapsychiatry.2024.4789.Peer-Reviewed Original ResearchAlcohol use disorderUse disorderPeak breath alcohol concentrationMedium to large effect sizesNon-treatment-seeking participantsWeeks of outpatient treatmentAlcohol self-administrationSelf-administration taskReduce alcohol intakeOnce-weekly subcutaneous semaglutideLarge effect sizesAlcohol consumptionSubsample of individualsBreath alcohol concentrationEffects of once-weekly subcutaneous semaglutideTreatment-by-time interactionOnce-weekly semaglutideAlcohol cravingReduce cravingSelf-administrationDrinking outcomesSemaglutide treatmentDrinking daysReduce drinkingAmount of alcoholEffects of psychedelics on opioid use disorder: a scoping review of preclinical studies
Pulido-Saavedra A, Oliva H, Prudente T, Kitaneh R, Nunes E, Fogg C, Funaro M, Weleff J, Nia A, Angarita G. Effects of psychedelics on opioid use disorder: a scoping review of preclinical studies. Cellular And Molecular Life Sciences 2025, 82: 49. PMID: 39833376, PMCID: PMC11747050, DOI: 10.1007/s00018-024-05519-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsOpioid use disorderUse disorderPreclinical studiesClinical studiesReview of preclinical studiesConditioned place preferenceOpioid self-administrationEffects of psychedelicsPreclinical in vivo studiesOpioid use disorder treatmentFrequency of administrationPlace preferencePotential therapeutic effectsSelf-administrationWithdrawal symptomsPreclinical findingsMechanism of actionSafety profilePain studiesPsychedelicsMethodological quality assessmentClinical evidenceCardiovascular riskOpioidWeb of ScienceDisruptions in Reward-Guided Decision-Making Functions Are Predictive of Greater Oral Oxycodone Self-Administration in Male and Female Rats
LaRocco K, Villiamma P, Hill J, Russell M, DiLeone R, Groman S. Disruptions in Reward-Guided Decision-Making Functions Are Predictive of Greater Oral Oxycodone Self-Administration in Male and Female Rats. Biological Psychiatry Global Open Science 2025, 5: 100450. PMID: 40083740, PMCID: PMC11904576, DOI: 10.1016/j.bpsgos.2025.100450.Peer-Reviewed Original ResearchAddiction-relevant behaviorsBiobehavioral mechanismsReward-guided decision-makingProbabilistic reversal-learning taskSaccharin fading procedureOxycodone self-administrationFemale Long-Evans ratsReversal-learning taskPathology of addictionFemale ratsTest of motivationDrug useLong-Evans ratsSuboptimal decision-makingOpioid use disorderSelf-administrationAddiction susceptibilityFading procedureEvans ratsSex differencesProblematic opioid useAdaptive decision-making processesDecision-making functionsAddictionDecision-making data
2024
Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats
Floris G, Zanda M, Dabrowski K, Daws S. Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats. Translational Psychiatry 2024, 14: 500. PMID: 39702361, PMCID: PMC11659471, DOI: 10.1038/s41398-024-03203-4.Peer-Reviewed Original ResearchConceptsResponse to heroinNucleus accumbensHeroin exposureOpioid use disorderSelf-administrationHeroin self-administrationMesolimbic dopamine systemOpioid-induced behaviorsMolecular neuroadaptationsDopamine systemOpioid rewardHeroin intakeBehavioral effectsUse disorderPsychiatric researchLipopolysaccharide (LPS)-induced neuroinflammationPreclinical modelsBehavioral ramificationsSensitivity to opioidsOpioid heroinHeroinMale ratsAccumbensHeightened immune responseNeuroinflammationPsilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats
Floris G, Dabrowski K, Zanda M, Daws S. Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats. Molecular Psychiatry 2024, 30: 1801-1816. PMID: 39433903, PMCID: PMC12015112, DOI: 10.1038/s41380-024-02788-y.Peer-Reviewed Original ResearchPrefrontal cortexHeroin seekingHeroin relapseDrug seekingSelf-administrationPrefrontal cortex of male ratsPrefrontal cortex of animalsCortex of male ratsHeroin self-administrationHeroin-seeking behaviorDrug-naive ratsOpioid-seeking behaviorSerotonin 2A receptorEfficacy of psilocybinAlcohol seekingHeroin takingForced abstinenceNucleus accumbensRelapse testRelapse behaviorIL-17AMaladaptive behaviorsPsychedelic compoundsAntagonist ketanserinPsilocybinPreclinical Evidence of the Effects of Sweet Flavors: Sweetness Increases Nicotine Intake and Seeking
Bagdas D, Addy N. Preclinical Evidence of the Effects of Sweet Flavors: Sweetness Increases Nicotine Intake and Seeking. Nicotine & Tobacco Research 2024, 27: 666-675. PMID: 39413033, DOI: 10.1093/ntr/ntae241.Peer-Reviewed Original ResearchNicotine use behaviorsNicotine reinforcementNicotine intakeSelf-administrationNicotine useFlavor exposureUse behaviorsIntravenous nicotine self-administrationPattern of nicotine intakeSessions of self-administrationNicotine self-administrationIncreased nicotine intakeNicotine-related behaviorsSaccharin-flavored solutionInfluence of early exposureSeeking behaviorNo significant sex differencesSignificant sex differencesImpact of early exposureSaccharin exposureEarly exposureFlavored solutionNicotine addictionSex differencesNicotineAstrocyte Ca2+ in the dorsal striatum suppresses neuronal activity to oppose cue-induced reinstatement of cocaine seeking
Tavakoli N, Malone S, Anderson T, Neeley R, Asadipooya A, Bardo M, Ortinski P. Astrocyte Ca2+ in the dorsal striatum suppresses neuronal activity to oppose cue-induced reinstatement of cocaine seeking. Frontiers In Cellular Neuroscience 2024, 18: 1347491. PMID: 39280793, PMCID: PMC11393831, DOI: 10.3389/fncel.2024.1347491.Peer-Reviewed Original ResearchCue-induced reinstatementCue-induced reinstatement of cocaine seekingCocaine self-administration experienceReinstatement of cocaine seekingCocaine self-administrationSelf-administer cocaineSelf-administration experimentsCocaine seekingDorsal striatumSelf-administrationExtinction of cocaine-seeking behaviorCocaine self-administration groupResponse to acute cocaineCocaine-seeking behaviorDorsal striatum neuronsDrug-seeking behaviorNeuronal activitySelf-administration groupLong-term neuronal plasticityBrain slicesAcute cocaineReward processingCocaine groupNeuronal signalingAcute administrationADVANCED CHARACTERIZATION OF ON- ELECTROCARDIOGRAPHIC (ECG) SENSORS’ DISCRIMINATORY POWER IN A HUMAN LABORATORY COCAINE SELF-ADMINISTRATION (SA) PARADIGM
Angarita G, Mayerson T, Pittman B, Nararajan A, Parate A, Marlin B, Gueorguieva R, Potenza M, Ganesan D, Malison R. ADVANCED CHARACTERIZATION OF ON- ELECTROCARDIOGRAPHIC (ECG) SENSORS’ DISCRIMINATORY POWER IN A HUMAN LABORATORY COCAINE SELF-ADMINISTRATION (SA) PARADIGM. Drug And Alcohol Dependence 2024, 260: 110014. DOI: 10.1016/j.drugalcdep.2023.110014.Peer-Reviewed Original ResearchPET 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 regionsComparison of Patient Health Questionnaire-9, Edinburgh Postnatal Depression Scale and Hospital Anxiety and Depression – Depression subscale scores by administration mode: An individual participant data differential item functioning meta-analysis
Harel D, Wu Y, Levis B, Fan S, Sun Y, Xu M, Rice D, Boruff J, Markham S, Ioannidis J, Takwoingi Y, Patten S, Ziegelstein R, Cuijpers P, Gilbody S, Vigod S, Akena D, Benedetti A, Thombs B, Azar M, Bhandari P, Chiovitti M, He C, Imran M, Krishnan A, Negeri Z, Neupane D, Riehm K, Yan X, Kloda L, Henry M, Ismail Z, Loiselle C, Mitchell N, Al-Adawi S, Alvarado R, Amtmann D, Arroll B, Ayalon L, Baradaran H, Barnes J, Beck K, Beck C, Bernstein C, Bindt C, Bombardier C, Boye B, Büel-Drabe N, Buji R, Bunevicius A, Butterworth P, Can C, Carter G, Chagas M, Chan J, Chan L, Chen C, Chibanda D, Chorwe-Sungani G, Clover K, Conroy R, Conway A, Conwell Y, Correa H, Castro e Couto T, Cukor D, Daray F, de Man-van Ginkel J, De Souza J, Downing M, Eapen V, Fann J, Favez N, Felice E, Fellmeth G, Ferentinos P, Fernandes M, Field S, Figueiredo B, Fischer F, Fisher J, Flint A, Fujimori M, Fung D, Gallagher P, Gandy M, Gelaye B, Gholizadeh L, Gibson L, Goodyear-Smith F, Grassi L, Green E, Greeno C, Hall B, Hantsoo L, Haroz E, Härter M, Hegerl U, Helle N, Hernando A, Hides L, Hobfoll S, Honikman S, Howard L, Hyphantis T, Iglesias-González M, Inagaki M, Jenewein J, Jeon H, Jetté N, Julião M, Kettunen P, Khamseh M, Kiely K, Kim S, Kjærgaard M, Kohlhoff J, Kohrt B, König H, Kozinszky Z, Kwan Y, Lamers F, Lara M, Leonardou A, Levin-Aspenson H, Liu S, Löbner M, Loosman W, Lotrakul M, Loureiro S, Love A, Löwe B, Luitel N, Lund C, Maes M, Malt U, Marrie R, Marsh L, Martínez P, Marx B, Matsuoka Y, McGuire A, Mehnert A, Michopoulos I, Sidik S, Müller-Nordhorn J, Muramatsu K, Radoš S, Navarrete L, Nelson C, Ng C, Nishi D, O'Donnell M, O'Rourke S, Osório F, Pabst A, Pasco J, Pawlby S, Peceliuniene J, Pence B, Persoons P, Petersen I, Picardi A, Ponsford J, Pugh S, Pulido F, Hernando A, Quinn T, Quispel C, Rathod S, Reme S, Reuter K, Riedel-Heller S, Rooney A, Santos I, Saracino R, Schellekens M, Schwarzbold M, Cankorur V, Shaaban J, Sharp D, Sharpe L, Shinn E, Sidebottom A, Simard S, Singer S, Skalkidou A, Smith-Nielsen J, Spangenberg L, Stafford L, Stein A, Stewart R, Strobel N, Su K, Sultan S, Sundström-Poromaa I, Sung S, Suzuki K, Tadinac M, Tan P, Tandon S, Taylor-Rowan M, Teixeira A, Tendais I, Tiringer I, Töreki A, Tran T, Trevillion K, Tschorn M, Turner A, Væver M, van der Feltz-Cornelis C, van Heyningen T, Vega-Dienstmaier J, Wagner M, Wagner L, Wang L, Wang J, Watson D, Weyerer S, White J, Whooley M, Wiese B, Williams L, Winkley K, Wynter K, Yamada M, Yonkers K, Zeng Q, Zhang Y. Comparison of Patient Health Questionnaire-9, Edinburgh Postnatal Depression Scale and Hospital Anxiety and Depression – Depression subscale scores by administration mode: An individual participant data differential item functioning meta-analysis. Journal Of Affective Disorders 2024, 361: 674-683. PMID: 38908554, DOI: 10.1016/j.jad.2024.06.033.Peer-Reviewed Original ResearchEdinburgh Postnatal Depression ScaleHospital Anxiety and Depression Scale depression subscalePatient Health Questionnaire-9Patient-reported outcome measuresDepression subscale scoresDepression subscaleInterviewer administrationHospital Anxiety and Depression Scale-depression subscale scorePostnatal Depression ScaleDepressive symptom scoresIntraclass correlation coefficientEvaluate depressive symptomsAdministration modeStatistically significant DIFDepression ScaleSelf-administrationIndicators multiple causes modelDepressive symptomsIn-personMedical settingsMultiple indicators multiple causes modelOutcome measuresPatient preferencesSubscale scoresMultiple causes modelSubstance use and spine density: a systematic review and meta-analysis of preclinical studies
Oliva H, Prudente T, Nunes E, Cosgrove K, Radhakrishnan R, Potenza M, Angarita G. Substance use and spine density: a systematic review and meta-analysis of preclinical studies. Molecular Psychiatry 2024, 29: 2873-2885. PMID: 38561468, PMCID: PMC11894807, DOI: 10.1038/s41380-024-02519-3.Peer-Reviewed Original ResearchSpine densityPrefrontal cortexSubstance useDrug self-administrationHippocampal spine densityEffects of cocaineSubstance use disordersConvergence of findingsSpine density changesSubstances of abuseMeta-analysis of preclinical studiesNucleus accumbensBehavioral sensitizationSelf-administrationBrain mechanismsPreclinical studiesBrain regionsMorphine effectsSynaptic density changesMeta-analysisAmphetamineSynaptic densityCocaineModerate-to-highCortexCocaine self-administration behavior is associated with subcortical and cortical morphometry measures in individuals with cocaine use disorder
Kohler R, Zhornitsky S, Potenza M, Yip S, Worhunsky P, Angarita G. Cocaine self-administration behavior is associated with subcortical and cortical morphometry measures in individuals with cocaine use disorder. The American Journal Of Drug And Alcohol Abuse 2024, 50: 345-356. PMID: 38551365, PMCID: PMC11305926, DOI: 10.1080/00952990.2024.2318585.Peer-Reviewed Original ResearchGray-matter volumeSelf-administer cocaineSelf-administration behaviorCocaine use disorderSelf-administrationGray-matterFrontal cortexUse disorderCocaine self-administration behaviorSelf-administered cocaine infusionsCocaine self-administrationSelf-administration paradigmInfusions self-administeredSelf-report assessmentsCortical brain regionsStructural MRI dataFR1 scheduleInsular thicknessCocaine infusionsPredisposing vulnerabilitiesCocaine consumptionCocaine useBrain regionsBilateral regionsLimbic system
2023
Orbitofrontal intronic circular RNA from Nrxn3 mediates reward learning and motivation for reward
Dabrowski K, Floris G, Gillespie A, Daws S. Orbitofrontal intronic circular RNA from Nrxn3 mediates reward learning and motivation for reward. Progress In Neurobiology 2023, 232: 102546. PMID: 38036039, PMCID: PMC10843848, DOI: 10.1016/j.pneurobio.2023.102546.Peer-Reviewed Original ResearchConceptsSucrose self-administrationOrbitofrontal cortexSelf-administrationReward behaviorBrain reward circuitryReward-seeking behaviorRegulating reward behaviorReward circuitryReward learningAppetitive rewardRewardSeeking behaviorRegulation of gene expressionMemoryNeurexin 3NRXN3Splicing factor SAM68MotivationRNA sequencingTranscriptome profilingLearningKnock-downCortexGene expressionBehaviorMicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration
Zanda M, Saikali L, Morris P, Daws S. MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration. Advances In Drug And Alcohol Research 2023, 3: 11668. PMID: 38389822, PMCID: PMC10880771, DOI: 10.3389/adar.2023.11668.Peer-Reviewed Original ResearchHeroin self-administrationOrbitofrontal cortexSelf-administrationDays of forced abstinenceRegulating drug-seeking behaviorSucrose self-administrationDrug-seeking behaviorChronic drug exposureAdult male ratsPeripheral blood samplesHeroin infusionsHeroin seekingMolecular neuroadaptationsForced abstinenceAcute abstinenceNeurobiological consequencesOpioid heroinOpioid misuseHeroinMale ratsSelf-administeredSeeking behaviorAbstinenceBlood samplesOpioid exposureTranscriptional signatures of heroin intake and relapse throughout the brain reward circuitry in male mice
Browne C, Futamura R, Minier-Toribio A, Hicks E, Ramakrishnan A, Martínez-Rivera F, Estill M, Godino A, Parise E, Torres-Berrío A, Cunningham A, Hamilton P, Walker D, Huckins L, Hurd Y, Shen L, Nestler E. Transcriptional signatures of heroin intake and relapse throughout the brain reward circuitry in male mice. Science Advances 2023, 9: eadg8558. PMID: 37294757, PMCID: PMC10256172, DOI: 10.1126/sciadv.adg8558.Peer-Reviewed Original ResearchConceptsOpioid use disorderHeroin intakeContext-induced drug-seekingBrain reward circuitryHeroin self-administrationRNA-seqDrug seekingReward circuitryGenome-wide association study dataSelf-administrationHeroin exposureDrug-takingIntegration of RNA-seq dataUse disorderPatterns of transcriptional regulationRNA-seq dataBehavioral outcomesMale miceMolecular changesTranscriptional regulationRegion-specificGene candidatesRNA sequencingHeroinBioinformatics analysis
2022
Heroin Regulates Orbitofrontal Circular RNAs
Floris G, Gillespie A, Zanda M, Dabrowski K, Sillivan S. Heroin Regulates Orbitofrontal Circular RNAs. International Journal Of Molecular Sciences 2022, 23: 1453. PMID: 35163373, PMCID: PMC8836038, DOI: 10.3390/ijms23031453.Peer-Reviewed Original ResearchConceptsHeroin self-administrationOrbitofrontal cortexOpioid use disorderNeurobiological adaptationsSelf-administrationSelf-administer sucroseChronic heroin exposureRat orbitofrontal cortexOpioid-seeking behaviorTreat opioid use disorderHeroin exposureUse disorderBrain regionsOpioid heroinBehavioral responsesMale ratsFemale ratsHeroinSeeking behaviorDrug overdose deathsRatsOverdose deathsOpioidRNA splice variantsCortex
2021
Drug-associated cues and drug dosage contribute to increased opioid seeking after abstinence
Zanda M, Floris G, Daws S. Drug-associated cues and drug dosage contribute to increased opioid seeking after abstinence. Scientific Reports 2021, 11: 14825. PMID: 34290298, PMCID: PMC8295307, DOI: 10.1038/s41598-021-94214-4.Peer-Reviewed Original ResearchConceptsDrug cuesDrug seekingIncubation of heroin cravingIncubation of opioid cravingDrug self-administration paradigmLow dose of heroinDrug-associated cuesSelf-administration paradigmDoses of heroinDays of abstinenceDrug-taking patternsDrug intake historyHeroin seekingRate of relapseHeroin cravingAbstinence phaseSelf-administrationOpioid cravingOpioid use disorderPromote relapseAbstinence lengthOpioid seekingUse disorderCompletion of rehabilitation programsIntake historyThe 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder
Bosse G, Cadeddu R, Floris G, Farero R, Vigato E, Lee S, Zhang T, Gaikwad N, Keefe K, Phillips P, Bortolato M, Peterson R. The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder. Journal Of Clinical Investigation 2021, 131 PMID: 33848264, PMCID: PMC8121512, DOI: 10.1172/jci143990.Peer-Reviewed Original ResearchConceptsOpioid use disorderOpioid self-administrationDehydroepiandrosterone sulfateSelf-administrationRat model of neuropathic painModel of neuropathic painTreatment of benign prostatic hyperplasiaUse disorderPotential of finasterideReduced self-administrationSelf-administration assayWithdrawal-induced hyperalgesiaBenign prostatic hyperplasiaEffects of finasterideSource of therapeutic targetsNeuropathic painOpioid withdrawalInhibitor finasterideSteroidogenesis inhibitorsProstatic hyperplasiaAntinociceptive effectTreatment optionsRat modelFinasterideMultiple opioids
2018
Sex and Feeding Status Differently Affect Natural Reward Seeking Behavior in Olfactory Bulbectomized Rats
Ruda-Kucerova J, Zanda M, Amchova P, Fratta W, Fattore L. Sex and Feeding Status Differently Affect Natural Reward Seeking Behavior in Olfactory Bulbectomized Rats. Frontiers In Behavioral Neuroscience 2018, 12: 255. PMID: 30425627, PMCID: PMC6218565, DOI: 10.3389/fnbeh.2018.00255.Peer-Reviewed Original ResearchSchedule of reinforcementPalatable food pelletsOBX ratsOBX lesionOperant respondingSelf-administrationFood pelletsNatural reward-seeking behaviorsIntravenous drug self-administrationSex differencesFood self-administrationDepressive-like phenotypeDrug self-administrationOperant self-administrationReward-seeking behaviorDrug-seeking behaviorRates of comorbidityPotential sex differencesFood restrictionOBX modelFood intakeOlfactory bulbectomyDrug-takingPalatable foodPsychiatric disorders
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