Featured Publications
Pharmacological modulation of the α7 nicotinic acetylcholine receptor in a mouse model of mecamylamine-precipitated nicotine withdrawal
Jackson A, Papke RL, Damaj MI. Pharmacological modulation of the α7 nicotinic acetylcholine receptor in a mouse model of mecamylamine-precipitated nicotine withdrawal. Psychopharmacology 2018, 235: 1897-1905. PMID: 29549391, PMCID: PMC6015775, DOI: 10.1007/s00213-018-4879-7.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsΑ7 nicotinic acetylcholine receptorMecamylamine-precipitated nicotine withdrawalNicotine withdrawal behaviorsNicotine withdrawalNicotinic acetylcholine receptorsSomatic signsPharmacological modulationNon-selective nAChR antagonist mecamylamineAcetylcholine receptorsNicotine withdrawal-induced hyperalgesiaWithdrawal-induced hyperalgesiaDose-related fashionNicotine withdrawal signsNAChR antagonist mecamylamineAnxiety-like behaviorAntagonist mecamylamineWithdrawal signsPreclinical dataNicotine rewardΑ7 nAChRsAgonist PNU282987Mouse modelWithdrawal behaviorAllosteric modulators
2022
Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice
Akinola LS, Bagdas D, Alkhlaif Y, Jackson A, Gurdap CO, Rahimpour E, Carroll FI, Papke RL, Damaj MI. Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice. Journal Of Psychopharmacology 2022, 36: 1280-1293. PMID: 36321267, PMCID: PMC9817006, DOI: 10.1177/02698811221132214.Peer-Reviewed Original ResearchConceptsNicotinic receptor agonistsReceptor agonistNicotinic acetylcholine receptorsLow sensitivityPharmacological characterizationΑ4β2 receptorsNicotine dependenceNicotinic subunitsPlace preferenceΑ4β2 nAChRsAcetylcholine receptorsPartial agonistFull agonistAgonistsDifferential efficacyBehavioral effectsNeurodegenerative diseasesSubtypesPathological conditionsNAChRsPotential targetPotential roleHypothermiaReceptorsΑ6
2021
Potentiation of (α4)2(β2)3, but not (α4)3(β2)2, nicotinic acetylcholine receptors reduces nicotine self-administration and withdrawal symptoms
Hamouda AK, Bautista MR, Akinola LS, Alkhlaif Y, Jackson A, Carper M, Toma WB, Garai S, Chen YC, Thakur GA, Fowler CD, Damaj MI. Potentiation of (α4)2(β2)3, but not (α4)3(β2)2, nicotinic acetylcholine receptors reduces nicotine self-administration and withdrawal symptoms. Neuropharmacology 2021, 190: 108568. PMID: 33878302, PMCID: PMC8169606, DOI: 10.1016/j.neuropharm.2021.108568.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsWithdrawal symptomsHypothermic effectMale miceAntinociceptive effectΑ4β2 nAChRsNicotine withdrawal-induced hyperalgesiaNAChR isoformsNicotine's antinociceptive effectsWithdrawal-induced hyperalgesiaNicotine withdrawal symptomsNicotine addiction treatmentAnxiety-like behaviorNicotinic acetylcholine receptorsDose-dependent mannerNociceptive responsesNicotine withdrawalNicotine intakeSomatic signsNicotine abstinencePharmacological effectsNicotine useAcetylcholine receptorsAffective symptomsPathophysiological processesN‐acylethanolamine‐hydrolysing acid amidase: A new potential target to treat paclitaxel‐induced neuropathy
Toma W, Caillaud M, Patel NH, Tran TH, Donvito G, Roberts J, Bagdas D, Jackson A, Lichtman A, Gewirtz DA, Makriyannis A, Malamas MS, Damaj MI. N‐acylethanolamine‐hydrolysing acid amidase: A new potential target to treat paclitaxel‐induced neuropathy. European Journal Of Pain 2021, 25: 1367-1380. PMID: 33675555, DOI: 10.1002/ejp.1758.Peer-Reviewed Original ResearchConceptsPaclitaxel-induced peripheral neuropathyPaclitaxel-induced mechanical hypersensitivityMechanical hypersensitivitySpinal cordSelective NAAA inhibitorsNAAA inhibitorsPEA levelsDevelopment of PIPNMajor dose-limiting side effectDose-limiting side effectAdministration of palmitoylethanolamidePaclitaxel-induced neuropathyPaclitaxel-treated micePaclitaxel-induced cytotoxicityEvidence of toleranceEffective chemotherapeutic agentIntrinsic rewarding effectsLung tumor cellsNew potential targetsEndogenous palmitoylethanolamidePain aversivenessAcute administrationPeripheral neuropathyControl micePEA administrationTargeting Peroxisome Proliferator-Activated Receptor-α (PPAR- α) to reduce paclitaxel-induced peripheral neuropathy
Caillaud M, Patel NH, White A, Wood M, Contreras KM, Toma W, Alkhlaif Y, Roberts JL, Tran TH, Jackson AB, Poklis J, Gewirtz DA, Damaj MI. Targeting Peroxisome Proliferator-Activated Receptor-α (PPAR- α) to reduce paclitaxel-induced peripheral neuropathy. Brain Behavior And Immunity 2021, 93: 172-185. PMID: 33434562, PMCID: PMC8226373, DOI: 10.1016/j.bbi.2021.01.004.Peer-Reviewed Original ResearchConceptsSensory nerve action potentialsPeripheral neuropathyCold hypersensitivityDevelopment of PNPaclitaxel-induced peripheral neuropathyPeroxisome Proliferator-Activated ReceptorsPaclitaxel-induced hypersensitivityTargeting Peroxisome ProliferatorEfficacy of fenofibrateRegulation of PPARSevere peripheral neuropathyNerve action potentialsExpression of PPARIL-6 mRNAInteresting therapeutic approachDecrease neuroinflammationCancer cell linesMechanical hypersensitivitySNAP amplitudeFenofibrate treatmentIL-1βDyslipidemia treatmentInflammatory responseTherapeutic approachesEffective treatment
2020
Impact of menthol on nicotine intake and preference in mice: Concentration, sex, and age differences
Bagdas D, Jackson A, Carper M, Chen RY, Akinola LS, Damaj MI. Impact of menthol on nicotine intake and preference in mice: Concentration, sex, and age differences. Neuropharmacology 2020, 179: 108274. PMID: 32827516, PMCID: PMC7572603, DOI: 10.1016/j.neuropharm.2020.108274.Peer-Reviewed Original ResearchConceptsOral nicotine consumptionEffect of mentholImpact of mentholNicotine consumptionFemale miceNicotine intakeΑ7 nicotinic acetylcholine receptorMenthol concentrationNicotine solutionHigher nicotine intakeAdolescent female miceMale C57BL/6J miceTwo-bottle choice paradigmWild-type miceNicotinic acetylcholine receptorsConcentration-dependent mannerOral nicotineC57BL/6J miceKO miceMale miceType miceMouse modelAcetylcholine receptorsHigh menthol concentrationAdult counterpartsRecent findings in the pharmacology of inhaled nicotine: Preclinical and clinical in vivo studies
Jackson A, Grobman B, Krishnan-Sarin S. Recent findings in the pharmacology of inhaled nicotine: Preclinical and clinical in vivo studies. Neuropharmacology 2020, 176: 108218. PMID: 32592708, PMCID: PMC7529934, DOI: 10.1016/j.neuropharm.2020.108218.Peer-Reviewed Original ResearchConceptsE-cigarettesVivo studiesNicotine productsCentral nervous system implicationsNon-combustible nicotine productsNicotine e-cigarettesLung injury casesPharmacokinetics of nicotineE-liquidsHeated tobacco productsTobacco product usersSearch engines PubMedProduct use-associated lung injury (EVALI) casesPharmacodynamic impactNon-combustible productsNicotine inhalerNicotine studiesMouse modelRodent modelsNicotine pharmacologyRodent studiesInjury casesPG/VGPharmacological impactNarrative review
2019
Impact of modulation of the α7 nicotinic acetylcholine receptor on nicotine reward in the mouse conditioned place preference test
Jackson A, Alkhlaif Y, Papke RL, Brunzell DH, Damaj MI. Impact of modulation of the α7 nicotinic acetylcholine receptor on nicotine reward in the mouse conditioned place preference test. Psychopharmacology 2019, 236: 3593-3599. PMID: 31302720, PMCID: PMC6895411, DOI: 10.1007/s00213-019-05331-y.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsΑ7 nicotinic acetylcholine receptorNicotine rewardNicotine CPPNicotinic acetylcholine receptorsΑ7 nAChRsAgonist PNU282987Acetylcholine receptorsPlace preference testMorphine CPPPharmacological modulationPharmacological agentsCPP paradigmPlace preferenceAllosteric modulatorsPNU282987MethodsThe effectsΑ7Beneficial effectsMiceSilent agonistPNU120596ObjectivesThis studyNS1738NS6740The α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal
Toma W, Kyte SL, Bagdas D, Jackson A, Meade JA, Rahman F, Chen ZJ, Del Fabbro E, Cantwell L, Kulkarni A, Thakur GA, Papke RL, Bigbee JW, Gewirtz DA, Damaj MI. The α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal. Experimental Neurology 2019, 320: 113010. PMID: 31299179, PMCID: PMC6708482, DOI: 10.1016/j.expneurol.2019.113010.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyPeripheral neuropathyNicotine rewardPaclitaxel treatmentRewarding effectsTreatment of CIPNPaclitaxel-induced mechanical hypersensitivityTumor-bearing NSG micePaclitaxel-induced peripheral neuropathyNon-small cell lung cancer cell linesCell lung cancer cell linesA549 non-small cell lung cancer cell lineMecamylamine-precipitated withdrawalAntitumor activityIntraepidermal nerve fibersLung cancer cell linesLung tumor growthNSCLC cell viabilityTumor-bearing miceIntrinsic rewarding effectsPlace preference testCancer cell linesConditioned place preference testMechanical hypersensitivityAgonist RThe β3 subunit of the nicotinic acetylcholine receptor is required for nicotine withdrawal-induced affective but not physical signs or nicotine reward in mice
Jackson AB, Toma W, Contreras KM, Alkhlaif Y, Damaj MI. The β3 subunit of the nicotinic acetylcholine receptor is required for nicotine withdrawal-induced affective but not physical signs or nicotine reward in mice. Pharmacology Biochemistry And Behavior 2019, 183: 1-5. PMID: 31145916, PMCID: PMC7197262, DOI: 10.1016/j.pbb.2019.05.003.Peer-Reviewed Original ResearchConceptsNicotine withdrawal signsWithdrawal signsNicotine rewardNicotinic acetylcholine receptorsWT miceNicotine dependenceAcetylcholine receptorsNicotine dependence behaviorsNicotine-dependent miceAffective nicotine withdrawal signsΒ3 subunitTobacco use disorderNicotine-induced CPPSimilar somatic symptomsPlace preference testNew molecular targetsAffective withdrawal signsAddictive componentSpontaneous withdrawalWithdrawal studyKO miceFemale miceHealth burdenPhysical signsUse disorders
2018
Knockout of alpha 5 nicotinic acetylcholine receptors subunit alters ethanol-mediated behavioral effects and reward in mice
Dawson A, Wolstenholme JT, Roni MA, Campbell VC, Jackson A, Slater C, Bagdas D, Perez EE, Bettinger JC, De Biasi M, Miles MF, Damaj MI. Knockout of alpha 5 nicotinic acetylcholine receptors subunit alters ethanol-mediated behavioral effects and reward in mice. Neuropharmacology 2018, 138: 341-348. PMID: 29944862, PMCID: PMC6400055, DOI: 10.1016/j.neuropharm.2018.06.031.Peer-Reviewed Original ResearchConceptsΑ5 nAChREthanol consumptionΑ5 nicotinic acetylcholine receptor (nAChR) subunitsAlcohol dependenceBehavioral effectsImportance of nAChRsΑ5 nAChR subunitΑ5-KO miceNicotinic acetylcholine receptor subunitsEthanol-induced hypothermiaAnxiolytic-like responseEthanol drinking behaviorVoluntary ethanol consumptionNicotinic acetylcholine receptorsΑ5 knockout miceAcetylcholine receptor subunitsTwo-bottle choiceDecreases ethanol intakePlace preference assayEthanol-induced behaviorsWild-type controlsKO miceRestraint stressDID paradigmEthanol intakeNew insights on the effects of varenicline on nicotine reward, withdrawal and hyperalgesia in mice
Bagdas D, Alkhlaif Y, Jackson A, Carroll FI, Ditre JW, Damaj MI. New insights on the effects of varenicline on nicotine reward, withdrawal and hyperalgesia in mice. Neuropharmacology 2018, 138: 72-79. PMID: 29860196, PMCID: PMC6054891, DOI: 10.1016/j.neuropharm.2018.05.025.Peer-Reviewed Original ResearchConceptsEffects of vareniclineNicotine withdrawal signsNicotine rewardΑ5 nAChRWithdrawal signsHigh doseKnockout miceΒ2-nAChRsNicotine withdrawal-induced hyperalgesiaAdministration of vareniclineWithdrawal-induced hyperalgesiaΑ7 knockout miceDose-related mannerNicotinic acetylcholine receptorsΑ5 knockout micePlace preference testVarenicline doseCessation treatmentNicotine withdrawalSomatic signsVareniclineΑ7 nAChRsMouse modelCPP testNicotinic subtypesN-Oleoyl-glycine reduces nicotine reward and withdrawal in mice
Donvito G, Piscitelli F, Muldoon P, Jackson A, Vitale RM, D'Aniello E, Giordano C, Ignatowska-Jankowska BM, Mustafa MA, Guida F, Petrie GN, Parker L, Smoum R, Sim-Selley L, Maione S, Lichtman AH, Damaj MI, Di Marzo V, Mechoulam R. N-Oleoyl-glycine reduces nicotine reward and withdrawal in mice. Neuropharmacology 2018, 148: 320-331. PMID: 29567093, PMCID: PMC6408981, DOI: 10.1016/j.neuropharm.2018.03.020.Peer-Reviewed Original ResearchConceptsTraumatic brain injuryNicotine-dependent miceNicotine addictionNicotine rewardInsular cortexWithdrawal responseNicotine CPPExperimental traumatic brain injuryPeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaPlace preference paradigmN-oleoyl glycineTobacco smokingMorphine CPPCigarette smokersIntraperitoneal administrationAntagonist GW6471Brain damageBrain injuryOlGlySystemic administrationRewarding effectsReceptor alphaMicePreference paradigm
2017
Assessment of nicotine withdrawal-induced changes in sucrose preference in mice
Alkhlaif Y, Bagdas D, Jackson A, Park AJ, Damaj IM. Assessment of nicotine withdrawal-induced changes in sucrose preference in mice. Pharmacology Biochemistry And Behavior 2017, 161: 47-52. PMID: 28919072, PMCID: PMC6408212, DOI: 10.1016/j.pbb.2017.08.013.Peer-Reviewed Original ResearchConceptsSucrose preference testNicotine withdrawalSpontaneous nicotine withdrawalLight-dark box testDark box testPositive affective stimuliSucrose preferenceAffective signsSmoking relapse ratesΑ6 KO miceSubcutaneous osmotic minipumpsWithdrawal-induced changesUnderlying neurobiological factorsPreference testRelapse rateOsmotic minipumpsKO miceTobacco useNicotine dependenceKnockout miceAnimal modelsNicotinic subunitsDay 15MiceDifferent dosesReversal of Nicotine Withdrawal Signs Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Male Mice
Hamouda AK, Jackson A, Bagdas D, Damaj M. Reversal of Nicotine Withdrawal Signs Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Male Mice. Nicotine & Tobacco Research 2017, 20: 903-907. PMID: 29059422, PMCID: PMC5991208, DOI: 10.1093/ntr/ntx183.Peer-Reviewed Original ResearchConceptsNicotine withdrawal symptomsSpontaneous nicotine withdrawalNicotine withdrawal signsNicotine withdrawalWithdrawal symptomsPositive allosteric modulatorsCessation aidWithdrawal signsMale miceMouse modelAllosteric modulatorsNicotinic acetylcholine receptor agonistNAChR-positive allosteric modulatorsAcetylcholine receptor agonistDose-dependent reversalICR male miceΑ4β2 nicotinic acetylcholine receptorsPositive allosteric modulationAnxiety-like behaviorNicotinic acetylcholine receptorsPotential clinical useAcute injectionRelapse rateTobacco smokingDay infusionAllosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain
Bagdas D, Ergun D, Jackson A, Toma W, Schulte M, Damaj M. Allosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain. European Journal Of Pain 2017, 22: 84-93. PMID: 28809075, PMCID: PMC9829446, DOI: 10.1002/ejp.1092.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsChronic neuropathic painNeuropathic painΑ4β2 nAChRsNicotinic acetylcholine receptorsAllosteric modulationAcetylcholine receptorsAntagonist dihydro-β-erythroidineNeuronal nicotinic acetylcholine receptorsChronic constriction injuryEndogenous cholinergic toneNicotine-evoked responsesAnimal pain modelsNicotine-induced antinociceptionDihydro-β-erythroidineMediation of painAlternative treatment strategiesBehavior doseConstriction injuryAntiallodynic effectPain modelPain modulationCholinergic tonePain behaviorAntinociceptive propertiesThe interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice
Donvito G, Bagdas D, Toma W, Rahimpour E, Jackson A, Meade JA, AlSharari S, Kulkarni AR, Carroll F, Lichtman AH, Papke RL, Thakur GA, Damaj M. The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice. Experimental Neurology 2017, 295: 194-201. PMID: 28606623, PMCID: PMC5558428, DOI: 10.1016/j.expneurol.2017.06.014.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAmidesAnimalsAzabicyclo CompoundsBenzamidesBridged Bicyclo CompoundsCannabinoid Receptor AntagonistsEthanolaminesFuransMaleMiceMice, Inbred ICRNicotinic AntagonistsNociceptionOxazolesPain MeasurementPalmitic AcidsPPAR alphaReceptor Cross-TalkSignal TransductionTyrosineConceptsPositive allosteric modulatorsAntinociceptive effectNicotinic acetylcholine receptorsΑ7 nAChRsAlpha 7 nicotinic acetylcholine receptorAcetylcholine receptorsNuclear peroxisome proliferator-activated receptorsΑ7 nicotinic acetylcholine receptorPeroxisome proliferator-activated receptorAnalgesic drug developmentProliferator-activated receptorAttenuated formalinAntinociceptive responseFormalin testΑ7 agonistsAntagonist SR144528Nociceptive behaviorTonic painBrain levelsAntagonist GW6471Exogenous administrationΑ7 nicotinicMouse modelCannabinoid CBOrthosteric agonistsIn vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence
Jackson A, Bagdas D, Muldoon PP, Lichtman AH, Carroll FI, Greenwald M, Miles MF, Damaj MI. In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence. Neuropharmacology 2017, 118: 38-45. PMID: 28279662, PMCID: PMC5410388, DOI: 10.1016/j.neuropharm.2017.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnesthetics, LocalAnimalsBenzamidesBridged Bicyclo CompoundsCocaineConditioning, OperantDisease Models, AnimalFenofibrateHypolipidemic AgentsMaleMiceMice, Inbred ICRNicotineNicotinic AgonistsOxazolesPPAR alphaPyrimidinesSelf AdministrationSubstance Withdrawal SyndromeTobacco Use DisorderTyrosineConceptsNicotine dependenceNicotinic acetylcholine receptorsNicotine rewardΑ7 nAChRsNicotine CPPWY-14643Acetylcholine receptorsRewarding propertiesNuclear peroxisome proliferator-activated receptorsΑ7 nicotinic acetylcholine receptorVentral tegmental area dopamine cellsEffect of α7Peroxisome proliferator-activated receptorNicotine withdrawal signsSmoking cessation therapyChronic tobacco useCurrent smoking cessation therapiesPPARα antagonist GW6471Main addictive componentPPARα-dependent mannerProliferator-activated receptorNicotine rewarding propertiesPlace preference testHomomeric α7 nAChRsSelf-administration model
2016
Oxycodone physical dependence and its oral self-administration in C57BL/6J mice
Enga RM, Jackson A, Damaj MI, Beardsley PM. Oxycodone physical dependence and its oral self-administration in C57BL/6J mice. European Journal Of Pharmacology 2016, 789: 75-80. PMID: 27393461, PMCID: PMC5824624, DOI: 10.1016/j.ejphar.2016.07.006.Peer-Reviewed Original ResearchConceptsConcentrations of oxycodonePost-prandial conditionsPhysical dependenceAntinociceptive effectPreclinical reportsPrescription opioidsAbused prescription opioidDoses of oxycodoneAbuse-related effectsOperant self-administration procedureSelf-administer waterSelf-administration procedureNumber of deliveriesOxycodone withdrawalNovel regimenOral oxycodoneNaloxone doseSomatic signsOxycodoneLimited access conditionsRegimenClinical useMiceOpioidsPositive reinforcerNicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse
Slater CA, Jackson A, Muldoon PP, Dawson A, O'Brien M, Soll LG, Abdullah R, Carroll FI, Tapper AR, Miles MF, Banks ML, Bettinger JC, Damaj IM. Nicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse. Alcohol Clinical And Experimental Research 2016, 40: 62-72. PMID: 26727524, PMCID: PMC4700556, DOI: 10.1111/acer.12918.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsAzetidinesBody TemperatureCentral Nervous System DepressantsDrug InteractionsEthanolHypnotics and SedativesHypothermiaKetamineMecamylamineMiceMice, Inbred C57BLMice, Inbred DBAMice, KnockoutNicotineNicotinic AgonistsNicotinic AntagonistsPentobarbitalPyridinesReceptors, NicotinicReflex, RightingVareniclineConceptsHypnotic effectsLORR testEtOH intakeReceptor efficacyAcute nicotine injectionDuration of EtOHNicotinic acetylcholine receptor subtypesΑ7 knockout miceNicotinic partial agonist vareniclineAcetylcholine receptor subtypesEffects of nicotineNicotinic antagonist mecamylamineDevelopment of toleranceEffects of EtOHPartial agonist vareniclineAcute injectionAcute nicotineNicotine administrationNicotine exposureAntagonist mecamylamineNicotine injectionHypothermic effectNicotine effectsHypnotic propertiesPharmacological interactions