2022
ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms
Mineur YS, Mose TN, Maibom KL, Pittenger ST, Soares AR, Wu H, Taylor SR, Huang Y, Picciotto MR. ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms. Molecular Psychiatry 2022, 27: 4918-4927. PMID: 36050437, PMCID: PMC10718266, DOI: 10.1038/s41380-022-01749-7.Peer-Reviewed Original ResearchConceptsBasolateral amygdalaBLA neuronsBalance of inhibitoryHuman mood disordersLight-dark boxGABA interneuronsPV neuronsVIP neuronsCalmodulin-dependent protein kinase IIMale miceACh levelsMood disordersTail suspensionNeuronal activityNeuron subtypesAcetylcholineChronic stressInhibitory signalingBalance of activityHomeostatic functionsBLA activityStress-induced changesNeuronsSocial defeatProtein kinase IIPositive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear
Lee B, Pothula S, Wu M, Kang H, Girgenti MJ, Picciotto MR, DiLeone RJ, Taylor JR, Duman RS. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Molecular Psychiatry 2022, 27: 2580-2589. PMID: 35418600, PMCID: PMC9135632, DOI: 10.1038/s41380-022-01498-7.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderFear extinctionInfralimbic medial prefrontal cortexFear conditioning modelEnhanced fear extinctionFear-based behaviorsProlonged stress modelMedial prefrontal cortexSpontaneous recoveryIL-mPFCPTSD modelPTSD treatmentStress disorderPrefrontal cortexSPS modelN-methyl-D-aspartate receptor modulatorsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsBehavioral effectsIncreased attentionMPFCPreclinical findingsPyramidal neuronsNeurotrophic factorMale mice
2020
Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses
Fogaça MV, Wu M, Li C, Li XY, Picciotto MR, Duman RS. Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses. Molecular Psychiatry 2020, 26: 3277-3291. PMID: 33070149, PMCID: PMC8052382, DOI: 10.1038/s41380-020-00916-y.Peer-Reviewed Original ResearchConceptsGABA interneuronsRapid antidepressant responseMajor depressive disorderAntidepressant effectsSynaptic plasticityAntidepressant responseRapid-acting antidepressantsAcetylcholine muscarinic receptor antagonistMuscarinic receptor antagonistCortical brain areasEffects of scopolamineAntidepressant actionChemogenetic inhibitionGABAergic interneuronsReceptor antagonistDepressive disorderMale miceInterneuron subtypesBrain areasInterneuronsMPFCTransient inhibitionAffective behaviorInhibitionSubtypesImpaired hypocretin/orexin system alters responses to salient stimuli in obese male mice
Tan Y, Hang F, Liu ZW, Stoiljkovic M, Wu M, Tu Y, Han W, Lee AM, Kelley C, Hajos M, Lu L, de Lecea L, de Araujo I, Picciotto M, Horvath TL, Gao XB. Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice. Journal Of Clinical Investigation 2020, 130: 4985-4998. PMID: 32516139, PMCID: PMC7456212, DOI: 10.1172/jci130889.Peer-Reviewed Original ResearchConceptsHcrt cellsObese miceDiet-induced obese miceObese male miceExcessive energy intakeNeuropeptide hypocretin/orexinHypocretin/orexinHcrt neuronsMale miceHcrt systemClinical studiesCommon causeSynaptic transmissionObese animalsEnergy intakeAcute stressCognitive functionSalient stimuliAlters responsesExact mechanismMiceHomeostatic regulationNeuronal networksBehavioral changesNeurons
2019
Perinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice
Lee AM, Picciotto MR. Perinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice. Behavioural Brain Research 2019, 367: 176-180. PMID: 30959127, PMCID: PMC6481625, DOI: 10.1016/j.bbr.2019.04.007.Peer-Reviewed Original ResearchConceptsNicotine exposureSingle-pellet reaching taskMotor tasksCortical synaptic plasticityPerinatal nicotine exposureDevelopmental nicotine exposureGross motor functionNicotine-treated animalsNicotine-induced changesFemale adult miceSkilled motor taskGross motor performanceAdverse outcomesMotor cortexFemale miceMale miceMotor functionSkilled forelimbPreclinical studiesControl animalsAdult miceImpaired learningSynaptic plasticityFemale pupsMorphologic changes
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 activityMenthol disrupts nicotine’s psychostimulant properties in an age and sex-dependent manner in C57BL/6J mice
Fait BW, Thompson DC, Mose TN, Jatlow P, Jordt SE, Picciotto MR, Mineur YS. Menthol disrupts nicotine’s psychostimulant properties in an age and sex-dependent manner in C57BL/6J mice. Behavioural Brain Research 2017, 334: 72-77. PMID: 28743602, PMCID: PMC5580257, DOI: 10.1016/j.bbr.2017.07.027.Peer-Reviewed Original ResearchConceptsAdult male miceNicotine intakeMale micePsychostimulant effectsPsychostimulant propertiesHome cage locomotor activitySex-dependent mannerSex-dependent mechanismsBlood levelsAdolescent miceFemale miceLocomotor stimulationLocomotor activityNicotine sensitivityAge groupsE-cigarettesMiceIntakeSignificant decreaseNicotineAgeSexBehavioral changesAdultsSpecific mechanismsAccess to nicotine in drinking water reduces weight gain without changing caloric intake on high fat diet in male C57BL/6J mice
Calarco CA, Lee S, Picciotto MR. Access to nicotine in drinking water reduces weight gain without changing caloric intake on high fat diet in male C57BL/6J mice. Neuropharmacology 2017, 123: 210-220. PMID: 28623168, PMCID: PMC5544033, DOI: 10.1016/j.neuropharm.2017.06.012.Peer-Reviewed Original ResearchConceptsHigh-fat dietCaloric intakeWeight gainFat dietFemale miceMale miceBody weightAdipose tissueEffects of HFDOverall caloric intakeAmphetamine-regulated transcriptNicotinic acetylcholine receptor subunitsLower body weightMelanin-concentrating hormoneSex-dependent mannerRegulation of agoutiChow-fed animalsAcetylcholine receptor subunitsNicotine administrationChronic consumptionArcuate nucleusNicotine dosesNicotine intakeFood intakeTobacco useHippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice
Mineur YS, Mose TN, Blakeman S, Picciotto MR. Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice. British Journal Of Pharmacology 2017, 175: 1903-1914. PMID: 28264149, PMCID: PMC5979617, DOI: 10.1111/bph.13769.Peer-Reviewed Original ResearchConceptsDepression-like behaviorNicotinic ACh receptorsFemale miceMale miceCholinergic signalingACh receptorsΑ7 nAChRsSignificant antidepressant-like effectΑ7 nicotinic ACh receptorsEffect of α7Antidepressant-like effectsAgonist GTS-21Depression-related behaviorsC-Fos immunoreactivityACh receptor antagonistDepression-like phenotypeAnxiety-like behaviorNicotinic acetylcholine receptorsAnxiety-like phenotypeHippocampal α7Physostigmine administrationAntagonist methyllycaconitineReceptor antagonistSwim testGTS-21
2014
Calcineurin Downregulation in the Amygdala Is Sufficient to Induce Anxiety-like and Depression-like Behaviors in C57BL/6J Male Mice
Mineur YS, Taylor SR, Picciotto MR. Calcineurin Downregulation in the Amygdala Is Sufficient to Induce Anxiety-like and Depression-like Behaviors in C57BL/6J Male Mice. Biological Psychiatry 2014, 75: 991-998. PMID: 24742621, PMCID: PMC4037359, DOI: 10.1016/j.biopsych.2014.03.009.Peer-Reviewed Original ResearchConceptsDepression-like behaviorOrgan transplant patientsAnxiety-like behaviorTransplant patientsMood disordersCalcineurin activityIncidence of anxietyCalcineurin inhibitor cyclosporine ALight/dark boxPotential clinical consequencesOpen field testSymptoms of anxietyChronic blockadeChronic administrationTransplant rejectionCsA treatmentRole of calcineurinSystemic inhibitionMale miceClinical consequencesCyclosporine ACalcineurin levelsBrain areasCalcium-dependent phosphatase calcineurinGene transfer approach
2008
Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice
Caldarone BJ, King SL, Picciotto MR. Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice. Neuroscience Letters 2008, 439: 187-191. PMID: 18524488, PMCID: PMC2491450, DOI: 10.1016/j.neulet.2008.05.023.Peer-Reviewed Original ResearchConceptsAnxiogenic-like responseChronic nicotineAnxiety-like behaviorLocomotor activationFemale miceLocomotor activityPsychostimulant propertiesChronic nicotine exposureFemale C57BL/6J miceSymptoms of anxietyNicotine variesNicotine exposureOverall incidenceC57BL/6J miceMale miceWildtype miceNicotine intakeNicotinic receptorsOpen armsHigh doseMiceNicotineAnxiety disordersBeta2 subunitBehavioral sensitivity