2019
Highs and lows of cannabinoid-dopamine interactions: effects of genetic variability and pharmacological modulation of catechol-O-methyl transferase on the acute response to delta-9-tetrahydrocannabinol in humans
Ranganathan M, De Aquino JP, Cortes-Briones JA, Radhakrishnan R, Pittman B, Bhakta S, D’Souza D. Highs and lows of cannabinoid-dopamine interactions: effects of genetic variability and pharmacological modulation of catechol-O-methyl transferase on the acute response to delta-9-tetrahydrocannabinol in humans. Psychopharmacology 2019, 236: 3209-3219. PMID: 31187152, DOI: 10.1007/s00213-019-05273-5.Peer-Reviewed Original ResearchConceptsCOMT rs4680 polymorphismMemory deficitsCOMT genotypeVal/Val individualsRs4680 polymorphismSubjective effectsTest dayCatechol-O-methyl transferase (COMT) enzymePsychotomimetic effectsCognitive effectsCognitive dataCannabinoid-dopamine interactionsAcute responseHuman brainIntravenous THCPlacebo-controlled studyRole of dopaminergicCatechol-O-methyl transferaseDopaminergic signalingAcute pharmacological inhibitionDeficitsCannabinoid effectsDopaminergic toneHealthy subjectsDrug development efforts
2016
Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO
Girgis RR, Slifstein M, D’Souza D, Lee Y, Periclou A, Ghahramani P, Laszlovszky I, Durgam S, Adham N, Nabulsi N, Huang Y, Carson RE, Kiss B, Kapás M, Abi-Dargham A, Rakhit A. Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO. Psychopharmacology 2016, 233: 3503-3512. PMID: 27525990, PMCID: PMC5035321, DOI: 10.1007/s00213-016-4382-y.Peer-Reviewed Original ResearchConceptsDopamine D3 receptorD2 receptorsD3 receptorsReceptor occupancyPartial agonistPositive symptomsD2 receptor partial agonistNegative symptomsPositron emission tomography scanDose-occupancy relationshipD2 receptor occupancyWeeks of dosingEmission tomography scanWeeks of treatmentExposure-response analysisReceptor partial agonistCerebrospinal fluid samplesDopamine D2 receptorsReward-related behaviorsD2 receptor ligandsTomography scanD2 antagonismPatientsDay 1Low dosesHuman Laboratory Studies on Cannabinoids and Psychosis
Sherif M, Radhakrishnan R, D’Souza D, Ranganathan M. Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry 2016, 79: 526-538. PMID: 26970363, DOI: 10.1016/j.biopsych.2016.01.011.BooksConceptsCannabinoid agonistsPsychotomimetic effectsAcute psychotomimetic effectsHealthy control subjectsCrossover laboratory studyEffects of ketamineHuman laboratory studiesGamma-aminobutyric acidHealthy human subjectsSelf-medication hypothesisTransient exacerbationAntipsychotic medicationControl subjectsDopamine metabolismGlutamate systemDopamine releasePsychotomimetic drugsCognitive symptomsDrug AdministrationAgonistsMagnitude of effectSymptomsSchizophreniaCannabinoidsLaboratory studies
2015
Deficits in Prefrontal Cortical and Extrastriatal Dopamine Release in Schizophrenia: A Positron Emission Tomographic Functional Magnetic Resonance Imaging Study
Slifstein M, van de Giessen E, Van Snellenberg J, Thompson JL, Narendran R, Gil R, Hackett E, Girgis R, Ojeil N, Moore H, D’Souza D, Malison RT, Huang Y, Lim K, Nabulsi N, Carson RE, Lieberman JA, Abi-Dargham A. Deficits in Prefrontal Cortical and Extrastriatal Dopamine Release in Schizophrenia: A Positron Emission Tomographic Functional Magnetic Resonance Imaging Study. JAMA Psychiatry 2015, 72: 316-324. PMID: 25651194, PMCID: PMC4768742, DOI: 10.1001/jamapsychiatry.2014.2414.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmphetamineCarbon RadioisotopesCase-Control StudiesDopamineDopamine AntagonistsFemaleFunctional NeuroimagingHumansMagnetic Resonance ImagingMaleMemory, Short-TermMesencephalonPositron-Emission TomographyPrefrontal CortexPyrrolidinesSalicylamidesSchizophreniaSchizophrenic PsychologyYoung AdultConceptsLevel-dependent functional magnetic resonanceBlood oxygenation level-dependent functional magnetic resonanceHealthy control individualsFunctional magnetic resonanceDopamine releaseExtrastriatal regionsPrefrontal cortexOutcome measuresAssociative striatumControl individualsAmphetamine-induced dopamine releaseBOLD activationNew York State Psychiatric InstituteDorsolateral PFCMagnetic resonance imaging studyPositron emission tomographic imagingStriatal dopamine releaseDrug-naive patientsFrontal cortical functionEffects of amphetamineExtrastriatal dopamine releaseResonance imaging studyFunctional magnetic resonance imaging studyEmission tomographic imagingMagnetic resonance
2005
Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function
Krystal JH, Perry EB, Gueorguieva R, Belger A, Madonick SH, Abi-Dargham A, Cooper TB, MacDougall L, Abi-Saab W, D’Souza D. Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function. JAMA Psychiatry 2005, 62: 985-995. PMID: 16143730, DOI: 10.1001/archpsyc.62.9.985.Peer-Reviewed Original Research
2000
Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT
Laruelle M, Abi-Dargham A, van Dyck C, Gil R, D’Souza D, Krystal J, Seibyl J, Baldwin R, Innis R. Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT. Biological Psychiatry 2000, 47: 371-379. PMID: 10704949, DOI: 10.1016/s0006-3223(99)00257-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsBrain StemCarrier ProteinsCase-Control StudiesCocaineDopamineDopamine Plasma Membrane Transport ProteinsFemaleHumansIodine RadioisotopesMaleMembrane GlycoproteinsMembrane Transport ProteinsMiddle AgedNeostriatumNerve Tissue ProteinsSchizophreniaSerotoninSerotonin Plasma Membrane Transport ProteinsTomography, Emission-Computed, Single-PhotonConceptsAmphetamine-induced dopamine releaseStriatal dopamine transporterDopamine transporterControl subjectsDAT densityDopamine releaseNegative symptomsStriatal DAT densityDuration of illnessDopamine nerve terminalsHealthy control subjectsSerotonin transporter densityCohort of subjectsRelative deficitSingle photon emissionNeurodegenerative processesPostmortem studiesNerve terminalsSerotonin functionTrend-level associationReceptor radiotracerPatientsDopamine functionLower striatalTransporter density
1999
Toward a rational pharmacotherapy of comorbid substance abuse in schizophrenic patients
Krystal J, D'Souza D, Madonick S, Petrakis I. Toward a rational pharmacotherapy of comorbid substance abuse in schizophrenic patients. Schizophrenia Research 1999, 35: s35-s49. PMID: 10190224, DOI: 10.1016/s0920-9964(98)00162-5.Peer-Reviewed Original ResearchConceptsSchizophrenic patientsSubstance abuseTerms of rehospitalizationComorbid substance abuseExacerbation of symptomsHealth care expensesSelf-medication hypothesisBetter prognosisMedical illnessPharmacotherapeutic approachesRational pharmacotherapyNonschizophrenic populationsPatientsVocational functionIllicit substancesCare expensesAbuseVulnerability hypothesisRehospitalizationExacerbationMedicationsPharmacotherapyPrognosisPsychostimulantsIllness
1997
Imaging D2 Receptor Occupancy by Endogenous Dopamine in Humans
Laruelle M, D’Souza C, Baldwin R, Abi-Dargham A, Kanes S, Fingado C, Seibyl J, Zoghbi S, Bowers M, Jatlow P, Charney D, Innis R. Imaging D2 Receptor Occupancy by Endogenous Dopamine in Humans. Neuropsychopharmacology 1997, 17: 162-174. PMID: 9272483, DOI: 10.1016/s0893-133x(97)00043-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAffectAlpha-MethyltyrosineAnimalsBenzamidesBrainDopamineEnzyme InhibitorsHomovanillic AcidHumansIodine RadioisotopesMaleMethoxyhydroxyphenylglycolParkinson Disease, SecondaryPyrrolidinesRatsRats, Sprague-DawleyReceptors, Dopamine D2Tomography, Emission-Computed, Single-PhotonTyrosine 3-MonooxygenaseConceptsAcute dopamine depletionSynaptic dopamine concentrationsEndogenous dopamineDopamine depletionPositron emission tomographyD2 receptorsTyrosine hydroxylase inhibitor alpha-methylDopamine concentrationsD2 receptor imagingD2 receptor upregulationD2 receptor occupancySingle photon emissionPara-tyrosineReceptor upregulationReceptor imagingAlpha-methylReceptor occupancyEmission tomographyDopaminePhoton emissionHuman brainReceptorsTomographyRodentsVivo measurements
1996
Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.
Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 9235-9240. PMID: 8799184, PMCID: PMC38625, DOI: 10.1073/pnas.93.17.9235.Peer-Reviewed Original ResearchConceptsAmphetamine-induced dopamine releaseDopamine releaseDopaminergic transmissionPsychotic symptomsSchizophrenic groupDopamine D2 receptor availabilityAmphetamine-induced decreaseAmphetamine-induced reductionD2 receptor availabilityD2 receptor radiotracerPositive psychotic symptomsSingle photon emissionExaggerated stimulationAbnormal responsivenessDopaminergic neuronsHealthy controlsReceptor radiotracerSchizophrenic patientsDopamine hypothesisDopamine functionReceptor availabilityAmphetamine effectsControl groupSchizophrenic subjectsSchizophrenia