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 roleHypothermiaReceptorsΑ6Persistent sensory changes and sex differences in transgenic mice conditionally expressing HIV-1 Tat regulatory protein
Toma W, Paris J, Warncke U, Nass S, Caillaud M, McKiver B, Ondo O, Bagdas D, Bigbee J, Knapp P, Hauser K, Damaj M. Persistent sensory changes and sex differences in transgenic mice conditionally expressing HIV-1 Tat regulatory protein. Experimental Neurology 2022, 358: 114226. PMID: 36096180, PMCID: PMC10053560, DOI: 10.1016/j.expneurol.2022.114226.Peer-Reviewed Original ResearchConceptsSensory neuropathyFemale miceHIV-1Tat expressionSensory nerve action potentialsIntraepidermal nerve fiber densityChronic HIV-1Persistent sensory changesPain-like behaviorsPeripheral sensory neuropathySevere chronic painDevelopment of neuropathyNerve fiber densityLumbar spinal cordDevelopment of hypersensitivityNerve action potentialsPrevious preclinical studiesDorsal root gangliaTNF-α expressionPPAR-α gene expressionTat regulatory proteinRole of TatHIV-1 TatSex differencesAllodynic responses
2021
(E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation
Bagdas D, Sevdar G, Gul Z, Younis R, Cavun S, Tae HS, Ortells MO, Arias HR, Gurun MS. (E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation. Neurological Research 2021, 43: 1056-1068. PMID: 34281483, DOI: 10.1080/01616412.2021.1949684.Peer-Reviewed Original ResearchConceptsPositive allosteric modulationΑ7 nAChRsNeuropathic painΑ7-selective antagonist methyllycaconitineΑ7 nicotinic acetylcholine receptorChronic constriction injuryPaw licking behaviorNeuropathic pain modelAcute systemic administrationChronic painful conditionsAntidepressant-like activityAnti-nociceptive activityDepression-like behaviorAnxiogenic-like effectsNicotinic acetylcholine receptorsAffective behaviorHuman α7 nAChRConstriction injuryMechanical allodyniaFormalin testPain modelAntagonist methyllycaconitineChronic painPainful conditionsRat α7 nAChRN‐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 administration
2020
Deficit in voluntary wheel running in chronic inflammatory and neuropathic pain models in mice: Impact of sex and genotype
Contreras KM, Caillaud M, Neddenriep B, Bagdas D, Roberts JL, Ulker E, White AB, Aboulhosn R, Toma W, Khalefa T, Adel A, Mann JA, Damaj MI. Deficit in voluntary wheel running in chronic inflammatory and neuropathic pain models in mice: Impact of sex and genotype. Behavioural Brain Research 2020, 399: 113009. PMID: 33181181, PMCID: PMC8961431, DOI: 10.1016/j.bbr.2020.113009.Peer-Reviewed Original ResearchConceptsNeuropathic pain modelChronic constriction injuryMechanical withdrawal thresholdPain modelStrains of miceWithdrawal thresholdDBA/2J miceVoluntary wheelChronic neuropathic pain modelPaclitaxel-treated miceVehicle-treated miceUnilateral intraplantar injectionLower mechanical thresholdsChronic pain reportQuality of lifeChemotherapy agent paclitaxelImpact of sexDifferent mouse strainsCCI miceCCI surgeryConstriction injuryIntraplantar injectionSham surgeryMale C57BL/6JNovel analgesicsImpact 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 counterpartsConditional expression of HIV‐1 tat in the mouse alters the onset and progression of tonic, inflammatory and neuropathic hypersensitivity in a sex‐dependent manner
Bagdas D, Paris J, Carper M, Wodarski R, Rice A, Knapp P, Hauser K, Damaj M. Conditional expression of HIV‐1 tat in the mouse alters the onset and progression of tonic, inflammatory and neuropathic hypersensitivity in a sex‐dependent manner. European Journal Of Pain 2020, 24: 1609-1623. PMID: 32533878, PMCID: PMC7856573, DOI: 10.1002/ejp.1618.Peer-Reviewed Original ResearchConceptsHIV-1 TatSex-dependent mannerFemale miceMechanical hypersensitivityAdjuvant injectionThermal hypersensitivityNeurotoxic HIV-1 regulatory proteinComplete Freund's adjuvant injectionChronic constrictive nerve injuryHIV sensory neuropathyNeuropathic nociceptive behaviorMagnitude of inflammationFreund's adjuvant injectionPeripheral nervous systemHIV-1 regulatory proteinHIV-1 proteinsAbility of TatSex differencesSequel of eventsNeuropathic hypersensitivityTat miceNerve injuryFormalin injectionPeripheral neuropathySensory neuropathy
2019
A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE
Godin J, Roy P, Quadri M, Bagdas D, Toma W, Narendrula-Kotha R, Kishta O, Damaj M, Horenstein N, Papke R, Simard A. A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE. Brain Behavior And Immunity 2019, 87: 286-300. PMID: 31874200, PMCID: PMC7604877, DOI: 10.1016/j.bbi.2019.12.014.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsSilent agonistInflammatory painCytokine productionΑ7 nAChRsAnimal modelsAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorNon-neuronal nAChRsExperimental autoimmune encephalomyelitisChronic inflammatory painAnti-inflammatory compoundsInflammation ex vivoChannel openingAutoimmune encephalomyelitisAntagonist mecamylamineMultiple sclerosisInflammatory disordersModulates inflammationMacrophage numbersDisease manifestationsNervous systemReceptor desensitizationInflammationAgonistsPharmacological mechanisms of alcohol analgesic-like properties in mouse models of acute and chronic pain
Neddenriep B, Bagdas D, Contreras K, Ditre J, Wolstenholme J, Miles M, Damaj M. Pharmacological mechanisms of alcohol analgesic-like properties in mouse models of acute and chronic pain. Neuropharmacology 2019, 160: 107793. PMID: 31562845, PMCID: PMC6924270, DOI: 10.1016/j.neuropharm.2019.107793.Peer-Reviewed Original ResearchConceptsAnalgesic-like propertiesComplete Freund's adjuvantAnti-nociceptive propertiesChronic painNeuropathic painChronic constriction injury modelAlcohol useMu-opioid systemOral ethanol administrationPain-like statePeripheral neuropathic painNeuropathic pain modelKappa-selective antagonistAcute alcohol useAnalgesic-like effectsDose-dependent reversalMechanical hypersensitivityAnalgesic effectNerve injuryPain modelAcute modelOpioid systemAcute alcoholFreund's adjuvantChronic useNeuropathic insult increases the responsiveness to acetic acid in mice.
Gurdap C, Markwalter P, Neddenriep B, Bagdas D, Damaj M. Neuropathic insult increases the responsiveness to acetic acid in mice. Behavioural Pharmacology 2019, 30: 534-537. PMID: 31033524, PMCID: PMC6684379, DOI: 10.1097/fbp.0000000000000486.Peer-Reviewed Original ResearchConceptsChronic constriction injuryChronic neuropathic painNeuropathic painPlace aversionAcute visceral painVehicle-treated micePeripheral nerve injuryPlace aversion (CPA) testPaclitaxel-treated animalsMillions of patientsCCI miceConstriction injuryVisceral painCCI animalsSham miceAcute painNerve injuryControl miceSciatic nerveNeuropathic insultMale miceNociceptive modelsPaclitaxel treatmentPainPlace conditioningAdolescent but not adult ethanol binge drinking modulates ethanol behavioral effects in mice later in life
Younis R, Wolstenholme J, Bagdas D, Bettinger J, Miles M, Damaj M. Adolescent but not adult ethanol binge drinking modulates ethanol behavioral effects in mice later in life. Pharmacology Biochemistry And Behavior 2019, 184: 172740. PMID: 31326461, PMCID: PMC6697373, DOI: 10.1016/j.pbb.2019.172740.Peer-Reviewed Original ResearchConceptsEthanol intakeEthanol drinkingEthanol's behavioral effectsEarly exposureAdolescent ethanol exposureEnhanced ethanol intakeAlcohol use disorderAnxiety-related behaviorAdolescence altersDrug-taking behaviorAlcohol intakeC57BL/6J miceEthanol exposureWithdrawal stateLong-term effectsNeurochemical mechanismsMouse modelBinge drinkingAdult miceUse disordersSerious illnessAbuse liabilityDrinking paradigmAdult exposureAdolescent populationThe 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 RAssessing nicotine dependence using an oral nicotine free-choice paradigm in mice
Bagdas D, Diester C, Riley J, Carper M, Alkhlaif Y, AlOmari D, Alayoubi H, Poklis J, Damaj M. Assessing nicotine dependence using an oral nicotine free-choice paradigm in mice. Neuropharmacology 2019, 157: 107669. PMID: 31220484, PMCID: PMC6697382, DOI: 10.1016/j.neuropharm.2019.107669.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AddictiveChoice BehaviorDose-Response Relationship, DrugDrug InteractionsFemaleMaleMiceMice, KnockoutNicotineNucleus AccumbensQuinineReceptors, NicotinicSelf AdministrationSex CharacteristicsSubstance Withdrawal SyndromeTobacco Use DisorderTyrosine 3-MonooxygenaseVareniclineConceptsAddictive-like propertiesNicotine intakeOral nicotine consumptionNicotine consumptionFree-choice paradigmNicotine solutionΑ6 KO miceTwo-bottle free-choice paradigmTyrosine hydroxylase levelsNicotinic acetylcholine receptor subunitsPartial agonist vareniclineOral nicotine intakeAbsence of nicotineAcetylcholine receptor subunitsΑ5 nAChRAdult C57BL/6JNicotine withdrawalKO miceFemale miceAgonist vareniclineDBA/2J miceHydroxylase levelsNicotine dependenceBinge drinkingObserved sex differencesC57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception
Bryant C, Bagdas D, Goldberg L, Khalefa T, Reed E, Kirkpatrick S, Kelliher J, Chen M, Johnson W, Mulligan M, Damaj M. C57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception. Molecular Pain 2019, 15: 1744806918825046. PMID: 30632432, PMCID: PMC6365993, DOI: 10.1177/1744806918825046.Peer-Reviewed Original ResearchConceptsAcute thermal nociceptionThermal nociceptionNerve injuryNociceptive behaviorPain modalitiesB6N miceAdjuvant modelComplete Freund's adjuvant (CFA) modelChronic constrictive nerve injuryBaseline mechanical thresholdInflammatory nociceptive behaviorsInflammatory nociceptive stimulusStrain differencesFreund's adjuvant modelDifferent pain modalitiesHot plate testPreclinical pain modelsHot plate sensitivityNeuropathic nociceptionNociceptive markersPaw diameterMechanical hypersensitivityInflammatory painNeuropathic painPain model
2018
Blockade of nicotinic acetylcholine receptor enhances the responsiveness to bupropion in the mouse forced swim test
Bagdas D, AlSharari S, Roni M, Campbell V, Muldoon P, Carroll F, Damaj M. Blockade of nicotinic acetylcholine receptor enhances the responsiveness to bupropion in the mouse forced swim test. Behavioural Brain Research 2018, 360: 262-269. PMID: 30552947, PMCID: PMC6324988, DOI: 10.1016/j.bbr.2018.12.027.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsImmobility timeWT miceDecreased immobility timeDihydro-β-erythroidineAdult male miceWild-type miceEffects of β2Nicotinic acetylcholine receptorsBaseline immobilityAntidepressant effectsPresent studyJ miceKO miceSwim testMale miceWT littermatesRole of α4Bupropion administrationBupropionAcute dosesFST behaviorTransgenic miceAcetylcholine receptorsNAChR subunitsEarly adolescent nicotine exposure affects later-life hippocampal mu-opioid receptors activity and morphine reward but not physical dependence in male mice
Kota D, Alajaji M, Bagdas D, Selley D, Sim-Selley L, Damaj M. Early adolescent nicotine exposure affects later-life hippocampal mu-opioid receptors activity and morphine reward but not physical dependence in male mice. Pharmacology Biochemistry And Behavior 2018, 173: 58-64. PMID: 30125591, PMCID: PMC6160313, DOI: 10.1016/j.pbb.2018.08.006.Peer-Reviewed Original ResearchConceptsMorphine rewardAdult miceG-protein activityNicotine exposurePhysical dependenceEarly adolescent nicotine exposureAdolescent nicotine treatmentMu-opioid receptor activityAdolescent nicotine exposureCurrent opioid crisisSomatic withdrawal signsMorphine physical dependenceDrug-taking behaviorNicotine treatmentWithdrawal signsWithdrawal symptomsMale miceLong-term effectsLow doseNicotine productsCPP testOpioid crisisReceptor activitySubstance abuseMiceMonoacylglycerol lipase inhibitors reverse paclitaxel-induced nociceptive behavior and proinflammatory markers in a mouse model of chemotherapy-induced neuropathy
Curry Z, Wilkerson J, Bagdas D, Kyte S, Patel N, Donvito G, Mustafa M, Poklis J, Niphakis M, Hsu K, Cravatt B, Gewirtz D, Damaj M, Lichtman A. Monoacylglycerol lipase inhibitors reverse paclitaxel-induced nociceptive behavior and proinflammatory markers in a mouse model of chemotherapy-induced neuropathy. Journal Of Pharmacology And Experimental Therapeutics 2018, 366: jpet.117.245704. PMID: 29540562, PMCID: PMC6038031, DOI: 10.1124/jpet.117.245704.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisBenzodioxolesBiomarkersCarbamatesCell Line, TumorCell ProliferationChemokine CCL2Disease Models, AnimalDose-Response Relationship, DrugEnzyme InhibitorsHumansHyperalgesiaInflammationMaleMiceMonoacylglycerol LipasesNociceptionP38 Mitogen-Activated Protein KinasesPaclitaxelPhosphoproteinsPiperidinesReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2SuccinimidesConceptsAntinociceptive effectPaclitaxel-induced mechanical allodyniaPaclitaxel-induced neuropathic painH460 non-small cell lung cancer cellsNon-small cell lung cancer cellsMonoacylglycerol lipaseMonocyte chemoattractant protein-1Chemotherapy-induced neuropathyPaclitaxel-induced allodyniaPain side effectsPrimary hydrolytic enzymesCell lung cancer cellsSpinal dorsal hornDorsal root gangliaChemoattractant protein-1Novel pharmacologic strategiesPaclitaxel-treated animalsNumerous rodent modelsLung cancer cellsPlace preference paradigmMonoacylglycerol lipase inhibitorsIntrinsic rewarding effectsPhospho-p38 MAPKMechanical allodyniaNeuropathic painCurcumin acts as a positive allosteric modulator of α7-nicotinic acetylcholine receptors and reverses nociception in mouse models of inflammatory pain
El Nebrisi E, Bagdas D, Toma W, Al Samri H, Brodzik A, Alkhlaif Y, Yang K, Howarth F, Damaj I, Oz M. Curcumin acts as a positive allosteric modulator of α7-nicotinic acetylcholine receptors and reverses nociception in mouse models of inflammatory pain. Journal Of Pharmacology And Experimental Therapeutics 2018, 365: jpet.117.245068. PMID: 29339457, PMCID: PMC7947331, DOI: 10.1124/jpet.117.245068.Peer-Reviewed Original ResearchConceptsEffect of curcuminPositive allosteric modulatorsMouse modelVisceral painAntinociceptive effectNACh receptorsAcetylcholine receptorsAllosteric modulatorsΑ7 nicotinic acetylcholine receptorVisceral pain modelHuman nicotinic acetylcholine receptorNicotinic acetylcholine receptorsInflammatory painPain modelNociceptive behaviorReceptor agonistSignificant potentiationDependent ClLocomotor activityACh concentrationPainNociceptionReceptorsTonicG proteins
2017
Nicotine prevents and reverses paclitaxel-induced mechanical allodynia in a mouse model of CIPN
Kyte S, Toma W, Bagdas D, Meade J, Schurman L, Lichtman A, Chen Z, Del Fabbro E, Fang X, Bigbee J, Damaj M, Gewirtz D. Nicotine prevents and reverses paclitaxel-induced mechanical allodynia in a mouse model of CIPN. Journal Of Pharmacology And Experimental Therapeutics 2017, 364: jpet.117.243972. PMID: 29042416, PMCID: PMC5738719, DOI: 10.1124/jpet.117.243972.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyPaclitaxel-induced mechanical allodyniaMechanical allodyniaPeripheral neuropathyMouse modelTreatment of CIPNLewis lung carcinoma tumor growthIntraepidermal nerve fiber lossPaclitaxel-induced peripheral neuropathyH460 non-small cell lung cancer cellsNon-small cell lung cancer cellsLung tumor cell proliferationNerve fiber dysfunctionNicotinic acetylcholine receptor subtypesCell lung cancer cellsChronic nicotine administrationNerve fiber lossChronic nicotine treatmentMale C57BL/6J miceAcetylcholine receptor subtypesLung cancer cellsProliferation of A549Receptor-mediated pathwayTumor cell proliferationCIPN treatmentAssessment 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 doses