2015
Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice
Mineur YS, Bentham MP, Zhou WL, Plantenga ME, McKee SA, Picciotto MR. Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice. Psychopharmacology 2015, 232: 3539-3549. PMID: 26146014, PMCID: PMC4561580, DOI: 10.1007/s00213-015-4001-3.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsPaired-pulse ratioC-Fos immunoreactivityPrefrontal cortexSwim testBrain areasRobust antidepressant-like effectsBrain regionsSex differencesMale C57BL/6J miceDepression-like behaviorEffects of guanfacineAcetylcholinesterase inhibitor physostigmineLight/dark boxBaseline sex differencesC-fos expressionDepression-like stateCritical brain regionsDifferent brain areasSex-specific changesAntidepressant efficacyCholinergic controlInhibitor physostigmineC57BL/6J miceAgonist guanfacine
2014
Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine
Mineur YS, Einstein EB, Bentham MP, Wigestrand MB, Blakeman S, Newbold SA, Picciotto MR. Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine. Neuropsychopharmacology 2014, 40: 938-946. PMID: 25288485, PMCID: PMC4330507, DOI: 10.1038/npp.2014.269.Peer-Reviewed Original ResearchMeSH Keywords8-Hydroxy-2-(di-n-propylamino)tetralinAlkaloidsAnimalsAntidepressive AgentsAzocinesDisease Models, AnimalDrug SynergismFluoxetineGene Expression RegulationHEK293 CellsHindlimb SuspensionHippocampusHumansInterpersonal RelationsMaleMiceMice, Inbred C57BLMotor ActivityQuinolizinesReceptor, Serotonin, 5-HT1ASelective Serotonin Reuptake InhibitorsSerotonin Receptor AgonistsStress, PsychologicalConceptsAntidepressant-like effectsSelective serotonin reuptake inhibitorsDorsal rapheCholinergic systemAgonist cytisineNicotinic acetylcholine receptor blockersEffects of cytisineTreatment-resistant patientsSerotonin reuptake inhibitorsAcetylcholine receptor blockerSSRI fluoxetineReceptor blockersAntidepressant efficacyReuptake inhibitorsSerotonin depletionCholinergic drugsMood disordersSerotonin receptorsMouse modelPharmacological approachesHippocampusReceptorsCytisineRapheMolecular mechanisms
2013
Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior
Mineur YS, Obayemi A, Wigestrand MB, Fote GM, Calarco CA, Li AM, Picciotto MR. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 3573-3578. PMID: 23401542, PMCID: PMC3587265, DOI: 10.1073/pnas.1219731110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholinesteraseAnimalsAntidepressive AgentsAnxietyBehavior, AnimalCholinergic AntagonistsCholinergic NeuronsDependovirusDepressionFluoxetineGene Knockdown TechniquesHindlimb SuspensionHippocampusHumansMaleMiceMice, Inbred C57BLPhenotypePhysostigmineReceptors, CholinergicResilience, PsychologicalRNA, Small InterferingSignal TransductionStress, PsychologicalTime FactorsConceptsDepression-like behaviorShRNA-mediated knockdownSelective serotonin reuptake inhibitor fluoxetineSerotonin reuptake inhibitor fluoxetineAChE inhibitor physostigmineAdministration of fluoxetineBlockade of acetylcholinesteraseEndophenotypes of depressionHippocampal AChE activityAntidepressant-like effectsReuptake inhibitor fluoxetineAChE activityDepression-like phenotypeSymptoms of depressionSocial defeat paradigmHippocampal AChEMuscarinic antagonistCholinergic drugsInhibitor physostigmineCholinergic systemClinical trialsSystemic administrationMood disordersSystemic effectsAnimal models
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 points
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 model
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
2006
The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not β2- or α7-nicotinic acetylcholine receptor subunit knockout mice
Rabenstein RL, Caldarone BJ, Picciotto MR. The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not β2- or α7-nicotinic acetylcholine receptor subunit knockout mice. Psychopharmacology 2006, 189: 395-401. PMID: 17016705, DOI: 10.1007/s00213-006-0568-z.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsAntagonist mecamylamineNicotinic acetylcholine receptor activityNoncompetitive nAChR antagonist mecamylamineAntagonist dihydro-β-erythroidineΑ7 knockout miceΑ7-nAChR subunitAcetylcholine receptor activityEffects of mecamylamineNAChR antagonist mecamylamineDihydro-β-erythroidineNicotinic antagonist mecamylamineSubunit knockout miceBaseline locomotor activityDose-response studyMethodsAdult miceAntagonist hexamethoniumAntidepressant efficacyAntidepressant responseCentral nAChRsImmobility timeCholinergic transmissionSwim testMecamylamineSuspension test
2004
High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation
Caldarone BJ, Harrist A, Cleary MA, Beech RD, King SL, Picciotto MR. High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation. Biological Psychiatry 2004, 56: 657-664. PMID: 15522249, DOI: 10.1016/j.biopsych.2004.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAmitriptylineAnalysis of VarianceAnimalsAntidepressive Agents, TricyclicBehavior, AnimalBromodeoxyuridineCell CountCell ProliferationDose-Response Relationship, DrugDrosophila ProteinsDrug InteractionsHelplessness, LearnedHindlimb SuspensionHippocampusImmunohistochemistryMecamylamineMiceMice, Inbred C57BLMice, KnockoutNeuronsNicotinic AntagonistsNortriptylineReceptors, NicotinicSwimmingConceptsHigh-affinity nAChRsHippocampal cell proliferationNicotinic acetylcholine receptorsSwim testAcetylcholine receptorsCell proliferationHigh-affinity nicotinic acetylcholine receptorsNoncompetitive nAChR antagonist mecamylamineAntagonism of nAChRsAntidepressant-induced increasesAntidepressant-like effectsNAChR antagonist mecamylamineWild-type miceInhibition of nAChRsAntidepressants actAntidepressant actionAntidepressant effectsChronic treatmentAntagonist mecamylamineAntidepressant propertiesTricyclic antidepressantsAntidepressant activityTherapeutic effectKnockout miceNoncompetitive antagonist
2003
Sex differences in response to oral amitriptyline in three animal models of depression in C57BL/6J mice
Caldarone BJ, Karthigeyan K, Harrist A, Hunsberger JG, Wittmack E, King SL, Jatlow P, Picciotto MR. Sex differences in response to oral amitriptyline in three animal models of depression in C57BL/6J mice. Psychopharmacology 2003, 170: 94-101. PMID: 12879206, DOI: 10.1007/s00213-003-1518-7.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsTail suspension testDuration of treatmentAntidepressant amitriptylineTransgenic miceChronic treatmentImmobility timeB6 miceDepression modelChronic AMI treatmentFemale B6 miceTricyclic antidepressant amitriptylineMechanism of actionAMI administrationOral amitriptylineAntidepressant treatmentControl miceLH paradigmSwim testFemale miceOral administrationAMI treatmentEscape latencySuspension testAnimal models