2023
A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model
Lv H, Catarino J, Li D, Liu B, Gao X, Horvath T, Huang Y. A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300015120. PMID: 37036983, PMCID: PMC10120042, DOI: 10.1073/pnas.2300015120.Peer-Reviewed Original ResearchConceptsVesicular GABA transporterActivity-based anorexiaExpression of AgRPNeuropeptide YAgRP neuronsAnorexia nervosaAnxiety/depressive-like behaviorsHypothalamic AgRP neuronsDepressive-like behaviorCurrent treatment optionsHigh relapse rateStress-related disordersHuman neuronal cellsNutritional supportRelapse rateTreatment optionsAnxiolytic effectsPsychiatric illnessMouse modelAnimal modelsHigh mortalityGABA transporterGenetic ablationNeuronal cellsNeurons
2022
TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons
Xie D, Stutz B, Li F, Chen F, Lv H, Sestan-Pesa M, Catarino J, Gu J, Zhao H, Stoddard CE, Carmichael GG, Shanabrough M, Taylor HS, Liu ZW, Gao XB, Horvath TL, Huang Y. TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons. Journal Of Clinical Investigation 2022, 132: e162365. PMID: 36189793, PMCID: PMC9525119, DOI: 10.1172/jci162365.Peer-Reviewed Original ResearchConceptsAgRP neuronsNeuropeptide YExpression of AgRPControl of feedingHypothalamic agoutiAnxiolytic effectsNeurotransmitter GABAMouse modelLeptin signalingStress-like behaviorsGenetic ablationNeuronsAgRPCritical central regulatorsEnergy expenditureGABAEnergy metabolismAppetiteFeedingCentral regulatorMetabolismCentral controlHuman cellsTET3Obesity
2020
AgRP neurons control compulsive exercise and survival in an activity-based anorexia model
Miletta MC, Iyilikci O, Shanabrough M, Šestan-Peša M, Cammisa A, Zeiss CJ, Dietrich MO, Horvath TL. AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nature Metabolism 2020, 2: 1204-1211. PMID: 33106687, DOI: 10.1038/s42255-020-00300-8.Peer-Reviewed Original ResearchConceptsAgRP neuronsActivity-based anorexia modelAgRP neuronal activityVivo fiber photometryFood-restricted miceFood-restricted animalsCompulsive exerciseAnorexia modelHypothalamic agoutiNeuropeptide YExercise volumeFood intakeMouse modelNeuronal activityFiber photometryDaily activationNeuronal circuitsPsychiatric conditionsAnorexia nervosaChemogenetic toolsNeuronsLong-term behavioral impactElevated fat contentVoluntary cessationFat content
2010
Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice
Gyengesi E, Liu ZW, D'Agostino G, Gan G, Horvath TL, Gao XB, Diano S. Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice. Endocrinology 2010, 151: 5395-5402. PMID: 20843996, PMCID: PMC2954711, DOI: 10.1210/en.2010-0681.Peer-Reviewed Original ResearchConceptsNPY/AgRP neuronsSynaptic input organizationSham-operated controlsAgRP neuronsADX miceCorticosterone replacementNeuropeptide YArcuate nucleusSynaptic arrangementsInput organizationPair-fed control animalsPutative excitatory synapsesPutative inhibitory synapsesHypothalamic arcuate nucleusEffects of adrenalectomySham-operated animalsNumber of synapsesPOMC neuronsProtein (AgRP) neuronsOrexigenic actionMembrane potentialSynaptic analysisInhibitory synapsesExcitatory synapsesFood intakeEnhanced anorexigenic signaling in lean obesity resistant syndecan-3 null mice
Zheng Q, Zhu J, Shanabrough M, Borok E, Benoit SC, Horvath TL, Clegg DJ, Reizes O. Enhanced anorexigenic signaling in lean obesity resistant syndecan-3 null mice. Neuroscience 2010, 171: 1032-1040. PMID: 20923696, PMCID: PMC2991621, DOI: 10.1016/j.neuroscience.2010.09.060.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAlpha-MSHAnalysis of VarianceAnimalsBody WeightDose-Response Relationship, DrugEatingFeeding BehaviorFood DeprivationGene Expression RegulationMaleMiceMice, KnockoutNeuronsNeuropeptide YParaventricular Hypothalamic NucleusProto-Oncogene Proteins c-fosSignal TransductionSyndecan-3Time FactorsConceptsMelanocortin agonist melanotan IISyndecan-3 null miceParaventricular nucleusBody weightNull miceHypothalamic target neuronsNeuropeptide α-MSHRisk of diabetesC-Fos immunoreactivityHypothalamic paraventricular nucleusBody weight regulationWild-type miceTypes of cancerAnorexigenic αAgRP neuronsHormone neuronsHypothalamic circuitsNeuropeptide YAnorexigenic signalingNeuropeptide responsesCardiovascular diseaseFood intakeTarget neuronsMelanotan IIType mice
2008
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL, Diano S. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature 2008, 454: 846-851. PMID: 18668043, PMCID: PMC4101536, DOI: 10.1038/nature07181.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsCarnitine O-PalmitoyltransferaseFatty AcidsFeeding BehaviorGene Expression RegulationGhrelinHypothalamusIon ChannelsMembrane Potential, MitochondrialMiceMitochondriaMitochondrial ProteinsNeuronsNeuropeptide YPhosphorylationReactive Oxygen SpeciesSynapsesUncoupling Protein 2ConceptsNPY/AgRP neuronsAgRP neuronsNeuronal activityCo-express neuropeptide YGut-derived hormone ghrelinAgRP neuronal activityArcuate nucleus neuronsFatty acid oxidation pathwayHypothalamic mitochondrial respirationG protein-coupled receptorsGhrelin actionNeuropeptide YNucleus neuronsHormone ghrelinFood intakeGhrelinFree radicalsSynaptic plasticityNeuronal functionIntracellular mechanismsNeuronsMitochondrial mechanismsProtein 2Mitochondrial proliferationRobust changesBsx, a Novel Hypothalamic Factor Linking Feeding with Locomotor Activity, Is Regulated by Energy Availability
Nogueiras R, López M, Lage R, Perez-Tilve D, Pfluger P, Mendieta-Zerón H, Sakkou M, Wiedmer P, Benoit SC, Datta R, Dong JZ, Culler M, Sleeman M, Vidal-Puig A, Horvath T, Treier M, Diéguez C, Tschöp M. Bsx, a Novel Hypothalamic Factor Linking Feeding with Locomotor Activity, Is Regulated by Energy Availability. Endocrinology 2008, 149: 3009-3015. PMID: 18308842, PMCID: PMC2408820, DOI: 10.1210/en.2007-1684.Peer-Reviewed Original ResearchConceptsHigh-fat dietArcuate nucleusLeptin resistanceMelanocortin-4 receptor knockout miceObese leptin-deficient miceAgouti gene-related proteinCentral nervous system controlNovel hypothalamic factorPeripheral energy balanceOrexigenic neuropeptide YReceptor knockout miceSpontaneous physical activityGhrelin receptor antagonistLeptin-deficient miceNervous system controlEnergy balance signalsFasting-induced increaseGene-related proteinGhrelin administrationLeptin injectionPharmacological modificationNeuropeptide YGhrelin signalingHypothalamic factorsReceptor antagonist
2007
A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2
Coppola A, Liu ZW, Andrews ZB, Paradis E, Roy MC, Friedman JM, Ricquier D, Richard D, Horvath TL, Gao XB, Diano S. A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2. Cell Metabolism 2007, 5: 21-33. PMID: 17189204, PMCID: PMC1783766, DOI: 10.1016/j.cmet.2006.12.002.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusEatingFastingFeeding BehaviorGreen Fluorescent ProteinsGuanosine DiphosphateHypothalamusIntercellular Signaling Peptides and ProteinsIodide PeroxidaseIon ChannelsMiceMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial ProteinsNeurogliaNeuronsNeuropeptide YProto-Oncogene Proteins c-fosThermogenesisTriiodothyronineUncoupling Protein 2ConceptsUncoupling protein 2Mitochondrial uncoupling protein 2Thyroid hormone productionProtein activityType 2 deiodinaseMitochondrial proliferationNeuropeptide YArcuate nucleusPhysiological roleMitochondrial uncouplingUCP2 activationProtein 2Hormone productionNPY/AgRP neuronsPhysiological significanceActive thyroid hormoneHypothalamic arcuate nucleusHypothalamic neuronal networksGlial cellsRebound feedingAgRP neuronsOrexigenic neuronsDeiodinaseDII activityPeripheral tissues
2006
Synaptic Plasticity in Energy Balance Regulation
Horvath TL. Synaptic Plasticity in Energy Balance Regulation. Obesity 2006, 14: 228s-233s. PMID: 17021372, DOI: 10.1038/oby.2006.314.Peer-Reviewed Original ResearchConceptsOb/ob miceNumber of excitatoryNeuropeptide YSynaptic plasticityPOMC neuronsOb miceFood intakeBehavioral effectsLeptin receptor-deficient miceRearrangement of synapsesLeptin-deficient miceReceptor-deficient miceHypothalamic arcuate nucleusOb/obEnergy balance regulationWild-type miceInfluences brain functionObserved synaptic plasticityWild-type animalsProopiomelanocortin neuronsAnorexigenic hormonesOrexigenic hormonePost-synaptic densityGlutamate inputsExtrahypothalamic sites
2005
Agouti-related peptide–expressing neurons are mandatory for feeding
Gropp E, Shanabrough M, Borok E, Xu AW, Janoschek R, Buch T, Plum L, Balthasar N, Hampel B, Waisman A, Barsh GS, Horvath TL, Brüning JC. Agouti-related peptide–expressing neurons are mandatory for feeding. Nature Neuroscience 2005, 8: 1289-1291. PMID: 16158063, DOI: 10.1038/nn1548.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsAnorexiaArcuate Nucleus of HypothalamusBeta-GalactosidaseBody WeightCell CountDiphtheria ToxinEatingFeeding BehaviorGene Expression RegulationIntercellular Signaling Peptides and ProteinsMiceMice, KnockoutNeuronsNeuropeptide YPro-OpiomelanocortinProteinsTime Factors
2004
Central Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats
Tang-Christensen M, Vrang N, Ortmann S, Bidlingmaier M, Horvath TL, Tschöp M. Central Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats. Endocrinology 2004, 145: 4645-4652. PMID: 15231700, DOI: 10.1210/en.2004-0529.Peer-Reviewed Original ResearchConceptsNeuropeptides neuropeptide YFood intakePhysical activityLocomotor activityOrexigenic neuropeptides neuropeptide YCentral administrationSpontaneous physical activitySingle intracerebroventricular injectionMajor etiological factorGH secretagogue receptorSpontaneous locomotor activityOverall locomotor activityDose-dependent mannerNovel peptide hormoneGhrelin injectionIntracerebroventricular injectionHypothalamic neuronsNeuropeptide YSecretagogue receptorEtiological factorsGhrelinHigh doseEndogenous ligandHunger factorAgRPRapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, Friedman JM, Horvath TL. Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin. Science 2004, 304: 110-115. PMID: 15064421, DOI: 10.1126/science.1089459.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArcuate Nucleus of HypothalamusBody WeightEatingEvoked PotentialsExcitatory Postsynaptic PotentialsFeeding BehaviorGamma-Aminobutyric AcidGhrelinGlutamic AcidGreen Fluorescent ProteinsIn Vitro TechniquesLeptinLuminescent ProteinsMiceMice, ObeseMice, TransgenicNeuronal PlasticityNeuronsNeuropeptide YPatch-Clamp TechniquesPeptide HormonesPro-OpiomelanocortinRecombinant Fusion ProteinsSynapsesTetrodotoxinTransgenesConceptsProopiomelanocortin neuronsNeuropeptide YFat-derived hormone leptinBehavioral effectsOb/ob miceLeptin-deficient miceOb/obHypothalamic arcuate nucleusWild-type miceNumber of excitatoryArcuate nucleusLeptin effectsPostsynaptic currentsOb miceHormone leptinSynaptic densityInhibitory synapsesFood intakeNeuronal typesLeptinMiceNeuronsFeeding circuitRapid rewiringHours
2003
The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis
Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu H, Pinto S, Colmers WF, Cone RD, Horvath TL. The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis. Neuron 2003, 37: 649-661. PMID: 12597862, DOI: 10.1016/s0896-6273(03)00063-1.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsCentral Nervous SystemCorticotropin-Releasing HormoneEnergy MetabolismFemaleGhrelinHomeostasisHypothalamusIn Vitro TechniquesIntercellular Signaling Peptides and ProteinsLuminescent ProteinsMiceMice, KnockoutMice, TransgenicNerve NetNeuronsNeuropeptide YOrgan SpecificityParaventricular Hypothalamic NucleusPatch-Clamp TechniquesPeptide HormonesPresynaptic TerminalsPro-OpiomelanocortinProtein BindingProtein BiosynthesisProteinsRatsConceptsCorticotropin-releasing hormoneNeuropeptide YNPY neuronsHypothalamic circuitsGastrointestinal peptide hormone ghrelinEffects of NPYEnergy homeostasisArcuate NPY neuronsRelease of ghrelinExpression of ghrelinMechanism of actionPeptide hormone ghrelinHypothalamic actionOrexigenic peptideHypothalamic nucleiHormone ghrelinParaventricular nucleusProopiomelanocortin (POMC) productsThird ventricleGhrelinPresynaptic terminalsElectrophysiological recordingsNeuronsHypothalamusHomeostasis
2001
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley M, Smart J, Rubinstein M, Cerdán M, Diano S, Horvath T, Cone R, Low M. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001, 411: 480-484. PMID: 11373681, DOI: 10.1038/35078085.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnimals, Genetically ModifiedAnorexiaArcuate Nucleus of HypothalamusElectrophysiologyEvoked PotentialsGamma-Aminobutyric AcidGreen Fluorescent ProteinsLeptinLuminescent ProteinsMaleMiceMice, Inbred C57BLNerve NetNeural InhibitionNeuronsNeuropeptide YPro-OpiomelanocortinConceptsAnorexigenic POMC neuronsPOMC neuronsArcuate nucleusLeptin actionLeptin-deficient humansLepob/Lepob miceLeptin receptor expressionLong-term energy balanceNonspecific cation channelGABA neuronsOrexigenic neuropeptidesObese humansAdipocyte hormoneNeuropeptide YLeptin resistanceElevated leptinReceptor expressionLepob miceMelanocortin peptidesTransgenic miceLeptinAction potentialsNeuropeptide modulatorsCommon obesityElectrophysiological recordings
2000
Mitochondrial Uncoupling Protein 2 (UCP2) in the Nonhuman Primate Brain and Pituitary*This work was supported by NSF Grant IBN-9728581, NIH Grants NS-36111, MH-59847, RR-00163, HD-29186, and HD-37186.
Diano S, Urbanski H, Horvath B, Bechmann I, Kagiya A, Nemeth G, Naftolin F, Warden C, Horvath T. Mitochondrial Uncoupling Protein 2 (UCP2) in the Nonhuman Primate Brain and Pituitary*This work was supported by NSF Grant IBN-9728581, NIH Grants NS-36111, MH-59847, RR-00163, HD-29186, and HD-37186. Endocrinology 2000, 141: 4226-4238. PMID: 11089557, DOI: 10.1210/endo.141.11.7740.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain ChemistryChlorocebus aethiopsCorticotropin-Releasing HormoneGene ExpressionHypothalamusImmunohistochemistryIn Situ HybridizationIon ChannelsLimbic SystemMacaca fascicularisMacaca mulattaMembrane Transport ProteinsMicroscopy, FluorescenceMitochondrial ProteinsNeuropeptide YOxytocinPituitary GlandPituitary Gland, AnteriorPituitary Gland, PosteriorProteinsRNA, MessengerUncoupling Protein 2VasopressinsConceptsUncoupling protein 2Pituitary glandAnterior lobePrimate brainAxonal processesBrain stem regionsNonhuman primate brainSitu hybridization histochemistryMessenger RNACentral autonomicRR-00163Mitochondrial uncoupling protein 2Neuropeptide YPrimate hypothalamusAnterior pituitaryMetabolic disordersRodent brainPosterior lobeHybridization histochemistryPOMC cellsCell bodiesUCP2 expressionRodent dataNovel targetBrainMitochondrial Uncoupling Protein 2 (UCP2) in the Nonhuman Primate Brain and Pituitary**This work was supported by NSF Grant IBN-9728581, NIH Grants NS-36111, MH-59847, RR-00163, HD-29186, and HD-37186.
Diano S, Urbanski H, Horvath B, Bechmann I, Kagiya A, Nemeth G, Naftolin F, Warden C, Horvath T. Mitochondrial Uncoupling Protein 2 (UCP2) in the Nonhuman Primate Brain and Pituitary**This work was supported by NSF Grant IBN-9728581, NIH Grants NS-36111, MH-59847, RR-00163, HD-29186, and HD-37186. Endocrinology 2000, 141: 4226-4238. DOI: 10.1210/en.141.11.4226.Peer-Reviewed Original ResearchUncoupling protein 2Pituitary glandPrimate brainIn situ hybridization histochemistryMitochondrial uncoupling protein 2Mitochondrial uncoupling proteinMessenger RNAGH-producing cellsNonhuman primate brainTreatment of metabolic disordersBrain stem regionsUncoupling protein 2 expressionAxonal processesRegulatory componentsUncoupling proteinPrimate hypothalamusPOMC cellsMetabolic regulationArcuate nucleusHybridization histochemistryAnterior pituitaryMitochondrial oxidationStem regionNeuropeptide YPeptide expressionEvidence of NPY Y5 receptor involvement in food intake elicited by orexin A in sated rats
Dube M, Horvath T, Kalra P, Kalra S. Evidence of NPY Y5 receptor involvement in food intake elicited by orexin A in sated rats. Peptides 2000, 21: 1557-1560. PMID: 11068104, DOI: 10.1016/s0196-9781(00)00311-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAppetite DepressantsAppetite RegulationCarrier ProteinsEatingFeeding BehaviorInjections, IntraventricularIntracellular Signaling Peptides and ProteinsMaleNaphthalenesNerve Tissue ProteinsNeuronsNeuropeptidesOrexin ReceptorsOrexinsPyrimidinesRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, NeuropeptideReceptors, Neuropeptide YSignal TransductionWeight GainConceptsOrexigenic peptideReceptor antagonistSated ratsNPY Y1 receptor antagonistNPY-producing neuronsPotent orexigenic peptideNPY Y5 receptor antagonistsY1 receptor antagonistY5 receptor antagonistsOrexin AIntracerebroventricular injectionY5 receptorsNeuropeptide YReceptor involvementFood intakeStimulate feedingNeuronsAntagonistRatsFeedingOrexinCurrent resultsFunctional linkHypothalamusNPYEvidence that NPY Y1 receptors are involved in stimulation of feeding by orexins (hypocretins) in sated rats
Jain M, Horvath T, Kalra P, Kalra S. Evidence that NPY Y1 receptors are involved in stimulation of feeding by orexins (hypocretins) in sated rats. Peptides 2000, 87: 19-24. PMID: 10710284, DOI: 10.1016/s0167-0115(99)00102-0.Peer-Reviewed Original ResearchConceptsNeuropeptide YLateral hypothalamic areaArcuate nucleusY1 receptorParaventricular nucleusSelective NPY Y1 receptor antagonistNPY Y1 receptor antagonistNPY Y1 receptorY1 receptor antagonistStimulation of feedingAdult male ratsDose-dependent mannerOrexigenic peptideOrexin ANPY receptorsExcitatory effectsHypothalamic areaHypothalamic appetiteReceptor antagonistMale ratsSated ratsOrexinNeural sitesReceptorsNPYergic
1999
Brain Uncoupling Protein 2: Uncoupled Neuronal Mitochondria Predict Thermal Synapses in Homeostatic Centers
Horvath T, Warden C, Hajos M, Lombardi A, Goglia F, Diano S. Brain Uncoupling Protein 2: Uncoupled Neuronal Mitochondria Predict Thermal Synapses in Homeostatic Centers. Journal Of Neuroscience 1999, 19: 10417-10427. PMID: 10575039, PMCID: PMC6782406, DOI: 10.1523/jneurosci.19-23-10417.1999.Peer-Reviewed Original ResearchConceptsC-Fos-expressing cellsPeripheral energy homeostasisHormone-releasing hormoneHypothalamic neuronal populationsCorticotropin-releasing factorMelanin-concentrating hormoneMitochondria of neuronsUCP2 proteinPeripheral hormonesProximal dendritesNeuropeptide YGonadal steroidsModulates neurotransmissionAxon terminalsBasal brainLocal brainNeuronal populationsAxonal processesNeuronal mitochondriaPeptidergic circuitsBrain circuitsEnergy homeostasisCold exposureNeuronsEndocrine processesInteractions between neuropeptide Y and gamma-aminobutyric acid in stimulation of feeding: a morphological and pharmacological analysis.
Pu S, Jain M, Horvath T, Diano S, Kalra P, Kalra S. Interactions between neuropeptide Y and gamma-aminobutyric acid in stimulation of feeding: a morphological and pharmacological analysis. Endocrinology 1999, 140: 933-40. PMID: 9927326, DOI: 10.1210/endo.140.2.6495.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidStimulation of feedingNeuropeptide YParaventricular nucleusFood intakeArcuate nucleusDose-related fashionEffects of muscimolFeeding responseRat brain sectionsNPY actionNPY terminalsNPY neuronsBrain stemHypothalamic controlReceptor agonistSecond messenger systemsSated ratsAxon terminalsBrain sectionsMagnocellular divisionMuscimolMorphological findingsPharmacological analysisDistinct receptors