2020
Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence
Hillmer AT, Angarita GA, Esterlis I, Anderson JM, Nabulsi N, Lim K, Ropchan J, Carson RE, Krystal JH, Malley S, Cosgrove KP. Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence. Neuropsychopharmacology 2020, 46: 380-385. PMID: 32919411, PMCID: PMC7852514, DOI: 10.1038/s41386-020-00856-9.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsSmoking statusAlcohol abstinenceEarly abstinenceMGlu5 receptor negative allosteric modulatorReceptor negative allosteric modulatorChronic alcohol useCortical brain regionsAlcohol use disorderEmission Tomography ImagingPositron emission tomography (PET) imagingNegative allosteric modulatorsDSM-5 criteriaCue-induced reinstatementHealthy controlsPreclinical literatureGlutamate systemPreclinical modelsHuman evidenceReceptor drugsPET scansUse disordersHuman studiesReceptor availabilityStudy durationPTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imaging
2019
Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET
Holmes SE, Gallezot JD, Davis MT, DellaGioia N, Matuskey D, Nabulsi N, Krystal JH, Javitch JA, DeLorenzo C, Carson RE, Esterlis I. Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 2254-2264. PMID: 31744389, PMCID: PMC7585925, DOI: 10.1177/0271678x19886316.Peer-Reviewed Original ResearchConceptsEffects of ketamineKetamine infusionGlutamate transmissionMetabotropic glutamate receptor 5Ketamine-induced effectsKetamine-induced changesGlutamate receptor 5Promising treatment targetDrug challenge studiesTwo-tissue compartment modelMGluR5 radioligandBlood pressureMGluR5 availabilityBaseline scanOutcome measuresHealthy subjectsHeart ratePsychiatric disordersReceptor 5Modulatory effectsMGluR5Treatment targetsChallenge studiesArterial input functionChallenge paradigm
2014
In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5
DeLorenzo C, DellaGioia N, Bloch M, Sanacora G, Nabulsi N, Abdallah C, Yang J, Wen R, Mann JJ, Krystal JH, Parsey RV, Carson RE, Esterlis I. In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5. Biological Psychiatry 2014, 77: 266-275. PMID: 25156701, PMCID: PMC4277907, DOI: 10.1016/j.biopsych.2014.06.024.Peer-Reviewed Original ResearchConceptsSubtype 5Ketamine administrationPET scansMetabotropic glutamate receptor subtype 5Prefrontal cortexAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced effectsPositron emission tomography (PET) ligandGlutamate receptor antagonistsVolume of distributionMedial prefrontal cortexNegative allosteric modulatorsKetamine initiationGlutamate releaseDorsal putamenKetamine responseSubanesthetic dosesOrbital prefrontal cortexReceptor antagonistAcute effectsBolus injectionDorsal caudateArterial bloodScan 1
2011
Rare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence
Xie P, Kranzler HR, Krauthammer M, Cosgrove KP, Oslin D, Anton RF, Farrer LA, Picciotto MR, Krystal JH, Zhao H, Gelernter J. Rare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence. Biological Psychiatry 2011, 70: 528-536. PMID: 21683344, PMCID: PMC3199609, DOI: 10.1016/j.biopsych.2011.04.017.Peer-Reviewed Original Research
2010
Decreased Beta2*‐nicotinic acetylcholine receptor availability after chronic ethanol exposure in nonhuman primates
Cosgrove KP, Kloczynski T, Bois F, Pittman B, Tamagnan G, Seibyl JP, Krystal JH, Staley JK. Decreased Beta2*‐nicotinic acetylcholine receptor availability after chronic ethanol exposure in nonhuman primates. Synapse 2010, 64: 729-732. PMID: 20340174, PMCID: PMC2904861, DOI: 10.1002/syn.20795.Peer-Reviewed Original ResearchConceptsChronic ethanol consumptionEthanol consumptionAlcohol consumptionNicotinic acetylcholine receptor availabilityAverage daily ethanol consumptionChronic ethanol exposureDaily ethanol consumptionEthanol-induced changesNicotinic acetylcholine receptorsSelf-administer ethanolIA-85380H withdrawalEthanol exposureReceptor availabilityAcetylcholine receptorsParietal cortexMale animalsTotal gramsBaselinePercent decreasePersistent changesWithdrawalMidbrainCortexAnimalsSPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals
Esterlis I, Cosgrove KP, Petrakis IL, McKee SA, Bois F, Krantzler E, Stiklus SM, Perry EB, Tamagnan GD, Seibyl JP, Krystal JH, Staley JK. SPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals. Drug And Alcohol Dependence 2010, 108: 146-150. PMID: 20074869, PMCID: PMC2871672, DOI: 10.1016/j.drugalcdep.2009.12.006.Peer-Reviewed Original ResearchConceptsDrinks/occasionNicotinic acetylcholine receptorsControl nonsmokersAcetylcholine receptorsHeavy drinkersHeavy drinkingLast alcoholic beverageHeavy alcohol drinkersHeavy alcoholSingle photon emissionSeverity of drinkingEffect of ageTobacco smokingAlcohol drinkersAlcohol drinkingCommon neural substrateNonsmokersAlcohol consumptionReceptor availabilityLarger studyAlcohol drinksAlcohol use behaviorsAddictive disordersDrinkersNeural substrates
2008
β 2 Nicotinic acetylcholine receptor availability in post-traumatic stress disorder
Czermak C, Staley JK, Kasserman S, Bois F, Young T, Henry S, Tamagnan GD, Seibyl JP, Krystal JH, Neumeister A. β 2 Nicotinic acetylcholine receptor availability in post-traumatic stress disorder. The International Journal Of Neuropsychopharmacology 2008, 11: 419-424. PMID: 18190729, DOI: 10.1017/s1461145707008152.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderClinician-Administered PTSD ScaleMesiotemporal cortexPTSD patientsPathophysiology of PTSDStress disorderBeta2 nAChRsNicotinic acetylcholine receptor availabilityHistory of smokingHealthy control subjectsNicotinic acetylcholine receptorsIA bindingNovel molecular targetsSingle photon emissionSubgroup of participantsRe-experiencing symptom clusterIA-85380Symptomatic patientsControl subjectsHealthy controlsReceptor availabilityPTSD ScaleAcetylcholine receptorsSymptom clustersPrefrontal cortex