2017
Bidirectional Regulation of Aggression in Mice by Hippocampal Alpha-7 Nicotinic Acetylcholine Receptors
Lewis AS, Pittenger ST, Mineur YS, Stout D, Smith PH, Picciotto MR. Bidirectional Regulation of Aggression in Mice by Hippocampal Alpha-7 Nicotinic Acetylcholine Receptors. Neuropsychopharmacology 2017, 43: 1267-1275. PMID: 29114104, PMCID: PMC5916354, DOI: 10.1038/npp.2017.276.Peer-Reviewed Original ResearchConceptsΑ7 nAChRsDentate gyrusNicotinic acetylcholine receptorsGTS-21Resident-intruder interactionsAlpha 7 nicotinic acetylcholine receptorAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorExcitatory-inhibitory balancePromising therapeutic interventionGranule cell activityAggressive behaviorResident-intruder testHippocampal α7Wild-type controlsUnderlying neurobiological substratesGABAergic interneuronsMale micePotential neural circuitsRegulation of aggressionGranule cellsTherapeutic interventionsPartial agonistBrain regionsCell activity
2013
Differential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule
Peng C, Stokes C, Mineur YS, Picciotto MR, Tian C, Eibl C, Tomassoli I, Guendisch D, Papke RL. Differential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule. Journal Of Pharmacology And Experimental Therapeutics 2013, 347: 424-437. PMID: 23959137, PMCID: PMC3807070, DOI: 10.1124/jpet.113.206904.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAnimalsAzocinesBehavior, AnimalBenzazepinesBrainBridged Bicyclo Compounds, HeterocyclicDose-Response Relationship, DrugDrug Partial AgonismHEK293 CellsHumansMaleMembrane PotentialsMiceMolecular StructureNicotinic AgonistsOocytesPatch-Clamp TechniquesQuinolizinesQuinoxalinesRatsRats, Sprague-DawleyReceptors, NicotinicTobacco Use DisorderVareniclineXenopus laevisConceptsPartial agonistLGN neuronsMouse tail suspension testLateral geniculate nucleus neuronsNicotinic acetylcholine receptor functionPartial agonist therapiesTail suspension testStratum radiatum interneuronsSmoking cessation drugNicotinic partial agonistAcetylcholine receptor functionHuman embryonic kidney 293 cellsSteady-state activationAgonist therapyRadiatum interneuronsEmbryonic kidney 293 cellsCessation drugsNucleus neuronsSuspension testΑ7 currentsNicotine addictionSide effectsVareniclineΑ4β2 nAChRsSR interneurons
2011
&agr;4&bgr;2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties
Mineur YS, Einstein EB, Seymour PA, Coe JW, O'Neill BT, Rollema H, Picciotto MR. &agr;4&bgr;2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties. Behavioural Pharmacology 2011, 22: 291-299. PMID: 21566524, PMCID: PMC3227135, DOI: 10.1097/fbp.0b013e328347546d.Peer-Reviewed Original ResearchConceptsNovelty-suppressed feeding testPartial agonistNicotinic acetylcholine receptor partial agonistAcceptable side effect profileAntidepressant-like effectsAntidepressant-like propertiesSide effect profileTail suspension testForced-swim testReceptor partial agonistLow intrinsic efficacyNicotinic acetylcholine receptorsAntidepressant efficacyFeeding testsReduced immobilityAntidepressant propertiesMood disordersNicotinic compoundsΑ4β2 nAChRsAcetylcholine receptorsLocomotor activityIntrinsic efficacyFunctional efficacySubtype selectivityTime pointsDissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380
Caldarone BJ, Wang D, Paterson NE, Manzano M, Fedolak A, Cavino K, Kwan M, Hanania T, Chellappan SK, Kozikowski AP, Olivier B, Picciotto MR, Ghavami A. Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380. Psychopharmacology 2011, 217: 199-210. PMID: 21487659, PMCID: PMC3266849, DOI: 10.1007/s00213-011-2271-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsAzetidinesBehavior, AnimalBenzazepinesBrainData Interpretation, StatisticalDose-Response Relationship, DrugLigandsMaleMiceMice, Inbred BALB CMice, Inbred C57BLMolecular StructureMotor ActivityNicotinic AgonistsProtein BindingPyridinesQuinoxalinesReceptors, NicotinicSwimmingTime FactorsVareniclineConceptsAntidepressant-like effectsAntidepressant-like actionSwim testDuration of actionReceptor occupancyNAChR antagonist mecamylamineDihydro-β-erythroidineAcetylcholine receptor agonistRole of β2Partial agonist vareniclineSymptoms of depressionNAChR β2Antagonist mecamylamineReceptor agonistActive dosesAgonist vareniclineSazetidinePartial agonistVareniclineObjectivesThe studyBehavioral efficacyNAChRsBehavioral responsesAgonistsPromising target
2009
Cytisine-Based Nicotinic Partial Agonists as Novel Antidepressant Compounds
Mineur YS, Eibl C, Young G, Kochevar C, Papke RL, Gündisch D, Picciotto MR. Cytisine-Based Nicotinic Partial Agonists as Novel Antidepressant Compounds. Journal Of Pharmacology And Experimental Therapeutics 2009, 329: 377-386. PMID: 19164465, PMCID: PMC2670591, DOI: 10.1124/jpet.108.149609.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAnimalsAntidepressive AgentsAzocinesCloning, MolecularData Interpretation, StatisticalElectrophysiologyEnvironmentFeeding BehaviorHindlimb SuspensionLaburnumMaleMiceMice, Inbred C57BLMotor ActivityNicotinic AgonistsOocytesPatch-Clamp TechniquesQuinolizinesReceptors, CholinergicSwimmingXenopus laevisConceptsAntidepressant-like effectsAntidepressant-like propertiesNicotinic partial agonistPartial agonistAntidepressant efficacyDose-dependent antidepressant-like effectNovelty-suppressed feeding testC57/BL6 miceBeta2 nAChRsAntidepressant-like activityTail suspension testBlood-brain barrierSelective partial agonistNicotinic acetylcholine receptorsNovel antidepressantsDevelopment of drugsBL6 miceAlpha3/beta4Alpha7 nAChRsAgonist effectsMood disordersRodent modelsSuspension testTail suspensionMouse modelVarenicline has antidepressant-like activity in the forced swim test and augments sertraline's effect
Rollema H, Guanowsky V, Mineur YS, Shrikhande A, Coe JW, Seymour PA, Picciotto MR. Varenicline has antidepressant-like activity in the forced swim test and augments sertraline's effect. European Journal Of Pharmacology 2009, 605: 114-116. PMID: 19168054, PMCID: PMC2707785, DOI: 10.1016/j.ejphar.2009.01.002.Peer-Reviewed Original ResearchConceptsAntidepressant-like activitySwim testPartial agonistNicotinic acetylcholine receptor activityNicotinic acetylcholine receptor partial agonistSelective serotonin reuptake inhibitor sertralineSerotonin reuptake inhibitor sertralineSelective serotonin reuptake inhibitorsAntidepressant-like propertiesAcetylcholine receptor activitySerotonin reuptake inhibitorsSmoking cessation aidReceptor partial agonistSertraline effectsVarenicline doseAntidepressant responseReuptake inhibitorsAntidepressant potentialCessation aidActive dosesAcetylcholine receptorsReceptor activityVareniclineMouse strainsAgonists
2007
Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice
Mineur YS, Somenzi O, Picciotto MR. Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice. Neuropharmacology 2007, 52: 1256-1262. PMID: 17320916, PMCID: PMC1959230, DOI: 10.1016/j.neuropharm.2007.01.006.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsAntidepressant-like propertiesAntidepressant efficacyNicotinic acetylcholine receptorsPartial agonistBasolateral amygdalaAcetylcholine receptorsHigh-affinity nicotinic acetylcholine receptorsC-Fos immunoreactivityNovel antidepressant drugsC-fos expressionPotential neurobiological correlatesAlpha3/Classical antidepressantsAntidepressant drugsRodent modelsImmunohistochemical analysisNeuronal activityAnimal modelsFull agonistAgonistsNeuronal systemsEfficacyNeurobiological correlatesCytisine