2024
L-type calcium channel regulation of depression, anxiety and anhedonia-related behavioral phenotypes following chronic stress exposure
Nunes E, Kebede N, Rajadhyaksha A, Addy N. L-type calcium channel regulation of depression, anxiety and anhedonia-related behavioral phenotypes following chronic stress exposure. Neuropharmacology 2024, 257: 110031. PMID: 38871116, PMCID: PMC11334593, DOI: 10.1016/j.neuropharm.2024.110031.Peer-Reviewed Original ResearchChronic unpredictable stressHome cage controlsElevated plus mazeForced swim testSucrose preference testCUS-induced decreaseChronic stress exposureImmobility timeStress exposureL-type calcium channelsDays of chronic unpredictable stressAnxiogenic-like behavioral responsesForced swim test immobility timeBehavioral responsesPre-existing mental health challengesAntidepressant-like responseOpen arm timeMood-related disordersRegulation of depressionExposure to chronic stressorsMale ratsL-type calcium channel blocker isradipineArm timePlus mazeSucrose preference
2023
Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders
Nunes E, Addy N, Conn P, Foster D. Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders. The Annual Review Of Pharmacology And Toxicology 2023, 64: 277-289. PMID: 37552895, PMCID: PMC10841102, DOI: 10.1146/annurev-pharmtox-051921-023858.Peer-Reviewed Original ResearchCholinergic neuronsMuscarinic acetylcholine receptor subtypesDA neuron activityMidbrain DA neuronsAcetylcholine receptor subtypesMood-related disordersPotential clinical implicationsDA circuitryDA neuronsDA releaseMuscarinic receptorsCholinergic regulationReceptor subtypesDopamine systemNeuron activityClinical implicationsNeuropsychiatric disordersDopamine signalingNumerous disordersSubtypesNumerous receptorsDisordersNeuronsReceptorsPublication dateVentral tegmental area M5 muscarinic receptors mediate effort-choice responding and nucleus accumbens dopamine in a sex-specific manner
Nunes E, Kebede N, Haight J, Foster D, Lindsley C, Conn P, Addy N. Ventral tegmental area M5 muscarinic receptors mediate effort-choice responding and nucleus accumbens dopamine in a sex-specific manner. Journal Of Pharmacology And Experimental Therapeutics 2023, 385: jpet-ar-2022-001438. PMID: 36828630, PMCID: PMC10108441, DOI: 10.1124/jpet.122.001438.Peer-Reviewed Original ResearchConceptsNucleus accumbens coreVentral tegmental areaM5 receptorsDA releaseMale ratsVTA infusionsDepressive disorderNucleus accumbensMuscarinic M5 receptorsSelective negative allosteric modulatorM5 muscarinic receptorsNegative allosteric modulatorsEffort-related choicePhasic DA releasePotential sex differencesSex-specific mannerACh toneVTA administrationCholinergic effectsMuscarinic receptorsFemale ratsTegmental areaPreclinical modelsDopamine releaseTherapeutic target
2022
L-type calcium channel regulation of dopamine activity in the ventral tegmental area to nucleus accumbens pathway: Implications for substance use, mood disorders and co-morbidities
Nunes E, Addy N. L-type calcium channel regulation of dopamine activity in the ventral tegmental area to nucleus accumbens pathway: Implications for substance use, mood disorders and co-morbidities. Neuropharmacology 2022, 224: 109336. PMID: 36414149, PMCID: PMC11215796, DOI: 10.1016/j.neuropharm.2022.109336.Peer-Reviewed Original ResearchConceptsL-type calcium channelsVentral tegmental areaPre-clinical modelsTegmental areaSubstance useLTCC blockersMood disordersCalcium channelsCo-morbid psychiatric diagnosesDA neuronal activityVoltage-gated calcium channelsMood-related behaviorsSubstance use disordersCalcium channel regulationStress-induced plasticityAccumbens pathwayCardiac medicationsDopamine neuronsLTCC subtypesNeuronal activityNeuronal firingUse disordersPsychiatric diagnosisCalcium entryDopamine activityCholinergic and dopaminergic‐mediated motivated behavior in healthy states and in substance use and mood disorders
Nunes EJ, Kebede N, Bagdas D, Addy NA. Cholinergic and dopaminergic‐mediated motivated behavior in healthy states and in substance use and mood disorders. Journal Of The Experimental Analysis Of Behavior 2022, 117: 404-419. PMID: 35286712, PMCID: PMC9743782, DOI: 10.1002/jeab.747.Peer-Reviewed Original ResearchConceptsMood disordersSubstance useActivational componentsMotivated behaviorComorbid substance useMesolimbic dopamine systemDA releaseCholinergic activityCholinergic transmissionImportant neuromodulatorCholinergic dysregulationDA regulationDopamine systemDA signalingActivational aspectsDisease statesDisordersAversive stimuliPossible roleHealthy stateCholinergicAcetylcholineStimuliEtiologyIllness
2021
Evaluation of Flavor Effects on Oral Nicotine Liking and/or Disliking Using the Taste Reactivity Test in Rats
Bagdas D, Rupprecht LE, Nunes EJ, Schillinger E, Immanuel JJ, Addy NA. Evaluation of Flavor Effects on Oral Nicotine Liking and/or Disliking Using the Taste Reactivity Test in Rats. Nicotine & Tobacco Research 2021, 24: 753-760. PMID: 34918123, PMCID: PMC8962681, DOI: 10.1093/ntr/ntab241.Peer-Reviewed Original ResearchConceptsTaste reactivity testOrosensory experienceAversive responsesAbuse liabilityAversive valueAversive reactionsHedonic responsesNicotine rewardTaking behaviorIntraoral cathetersImpact of mentholReactivity testOlfactory cuesOrofacial movementsDislikingLikingNicotine responseTaste stimuliSex-dependent mannerOral nicotineNicotine inducesNicotineCuesIngestive responsesExperience
2015
Dopamine/Adenosine Interactions Related to Tremor in Animal Models of Parkinsonism
Salamone J, Podurgiel S, Long L, Nunes E, Correa M. Dopamine/Adenosine Interactions Related to Tremor in Animal Models of Parkinsonism. Current Topics In Neurotoxicity 2015, 10: 149-162. DOI: 10.1007/978-3-319-20273-0_8.Peer-Reviewed Original ResearchAdenosine A2A receptor antagonistTremulous jaw movementsA2A receptor antagonistsAdenosine A2A receptorsAnimal modelsReceptor antagonistA2A receptorsAdenosine A2A receptor knockout miceA2A receptor knockout miceTremulous jaw movement modelAnti-tremor effectJaw movementsReceptor knockout miceHuman clinical studiesAdenosine A2A antagonistsAntiparkinsonian effectsCholinomimetic stimulationOral tremorIntrastriatal injectionDopamine depletionCGS 21680Antiparkinsonian agentsDopamine antagonistsClinical studiesA2A antagonistsExamination of Rapid Dopamine Dynamics with Fast Scan Cyclic Voltammetry During Intra-oral Tastant Administration in Awake Rats
Wickham R, Park J, Nunes E, Addy N. Examination of Rapid Dopamine Dynamics with Fast Scan Cyclic Voltammetry During Intra-oral Tastant Administration in Awake Rats. Journal Of Visualized Experiments 2015 DOI: 10.3791/52468-v.Peer-Reviewed Original Research
2014
The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs
Randall P, Lee C, Nunes E, Yohn S, Nowak V, Khan B, Shah P, Pandit S, Vemuri V, Makriyannis A, Baqi Y, Müller C, Correa M, Salamone J. The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs. PLOS ONE 2014, 9: e99320. PMID: 24937131, PMCID: PMC4061002, DOI: 10.1371/journal.pone.0099320.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsBenzazepinesBenzophenonesBupropionCannabinoid Receptor AntagonistsChoice BehaviorDepressionDopamine AntagonistsDrug Evaluation, PreclinicalFeeding BehaviorMaleNitrophenolsPyrazolesRats, Sprague-DawleySalicylamidesSelegilineTetrabenazineTolcaponeVesicular Monoamine Transport ProteinsXanthinesConceptsChow intakeAdenosine A2A antagonist MSX-3Vesicular monoamine transport (VMAT-2) inhibitor tetrabenazineCB1 receptor neutral antagonistsMAO-B inhibitor deprenylEffort-related decisionAppetite suppressant drugsVMAT-2 inhibitor tetrabenazineProgressive ratioDA antagonist haloperidolInhibitor tetrabenazineEffort-related effectsMSX-3High-carbohydrate foodsAntagonist haloperidolDepressed patientsMajor depressionAntidepressant drugsLab chowRodent modelsDepressive symptomsMotivational symptomsAnimal modelsSelective dopaminePsychomotor retardation
2013
Effort-Related Motivational Effects of the VMAT-2 Inhibitor Tetrabenazine: Implications for Animal Models of the Motivational Symptoms of Depression
Nunes E, Randall P, Hart E, Freeland C, Yohn S, Baqi Y, Müller C, López-Cruz L, Correa M, Salamone J. Effort-Related Motivational Effects of the VMAT-2 Inhibitor Tetrabenazine: Implications for Animal Models of the Motivational Symptoms of Depression. Journal Of Neuroscience 2013, 33: 19120-19130. PMID: 24305809, PMCID: PMC3850037, DOI: 10.1523/jneurosci.2730-13.2013.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine A2 Receptor AntagonistsAdrenergic Uptake InhibitorsAnimalsAntidepressive Agents, Second-GenerationBehavior, AnimalBupropionConditioning, OperantDepressionDisease Models, AnimalDopamineDopamine and cAMP-Regulated Phosphoprotein 32EnkephalinsFeeding BehaviorImmunohistochemistryMaleMicrodialysisMotivationNucleus AccumbensProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleySubstance PTetrabenazineVesicular Monoamine Transport ProteinsXanthinesConceptsMotivational symptomsAnimal modelsEffort-related choice behaviorAdenosine A2A antagonist MSX-3Vesicular monoamine transport (VMAT-2) inhibitor tetrabenazineEffort-related motivational effectsEffort-related motivational symptomsAccumbens medium spiny neuronsVMAT-2 inhibitor tetrabenazineD2 DA receptorsDepression-like effectsDose-related decreaseMedium spiny neuronsEffects of tetrabenazineInhibitor tetrabenazineEffort-related choiceEffort-related effectsDA receptorsAntidepressant bupropionChow intakeMSX-3Spiny neuronsMajor depressionExtracellular dopamineFood intakeEffort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task
Nunes E, Randall P, Estrada A, Epling B, Hart E, Lee C, Baqi Y, Müller C, Correa M, Salamone J. Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task. Psychopharmacology 2013, 231: 727-736. PMID: 24136220, PMCID: PMC4468782, DOI: 10.1007/s00213-013-3285-4.Peer-Reviewed Original ResearchConceptsPro-inflammatory cytokines interleukinIL-1βMotivational symptomsEffort-related choice behaviorCytokines interleukinLow dosesEffort-related motivational effectsEffort-related motivational symptomsPro-inflammatory cytokinesLoss of appetiteInvolvement of cytokinesAdministration of cytokinesRatio 5 leverSame dose rangeAdenosine A2A antagonistsEffort-related impairmentsCore body temperatureObjectivesThe present experimentsChow intakeMSX-3ResultsIL-1βAvailable chowFood intakeTendency of ratsA2A antagonistsS.2.1 - DEVELOPMENT OF ANIMAL MODELS OF THE EFFORT-RELATED SYMPTOMS OF DEPRESSION
Salamone J, Nunes E, Randall P, Yohn S, Merce C. S.2.1 - DEVELOPMENT OF ANIMAL MODELS OF THE EFFORT-RELATED SYMPTOMS OF DEPRESSION. Behavioural Pharmacology 2013, 24: e3. DOI: 10.1097/01.fbp.0000434686.35248.7a.Peer-Reviewed Original ResearchThe vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces tremulous jaw movements in rodents: Implications for pharmacological models of parkinsonian tremor
Podurgiel S, Nunes E, Yohn S, Barber J, Thompson A, Milligan M, Lee C, López-Cruz L, Pardo M, Valverde O, Lendent C, Baqi Y, Müller C, Correa M, Salamone J. The vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces tremulous jaw movements in rodents: Implications for pharmacological models of parkinsonian tremor. Neuroscience 2013, 250: 507-519. PMID: 23867769, DOI: 10.1016/j.neuroscience.2013.07.008.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic Uptake InhibitorsAnimalsCatalepsyData Interpretation, StatisticalDisease Models, AnimalDose-Response Relationship, DrugJawMaleMiceMice, KnockoutMotor ActivityMovementParkinsonian DisordersProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleyReceptor, Adenosine A2ATetrabenazineTremorVesicular Monoamine Transport ProteinsXanthinesConceptsTremulous jaw movementsVentrolateral neostriatumC-fos expressionMSX-3Receptor transmissionAdenosine A2A antagonist MSX-3A2A receptor knockout miceParkinsonian tremorC-Fos-positive cellsAbility of tetrabenazineParkinsonian side effectsVesicular monoamine storageJaw movementsReceptor knockout miceAdenosine A2A receptorsOral tremorWild-type controlsPharmacological antagonismStriatal dopamineLocomotor suppressionMotor effectsCD1 miceRodent modelsKnockout miceSide effectsNucleus accumbens neurotransmission and effort-related choice behavior in food motivation: Effects of drugs acting on dopamine, adenosine, and muscarinic acetylcholine receptors
Nunes E, Randall P, Podurgiel S, Correa M, Salamone J. Nucleus accumbens neurotransmission and effort-related choice behavior in food motivation: Effects of drugs acting on dopamine, adenosine, and muscarinic acetylcholine receptors. Neuroscience & Biobehavioral Reviews 2013, 37: 2015-2025. PMID: 23583616, DOI: 10.1016/j.neubiorev.2013.04.002.Peer-Reviewed Original ResearchConceptsEffort-related choice behaviorMuscarinic acetylcholine receptorsDA antagonismEffort-related processesNAc coreAcetylcholine receptorsFood motivationAspects of appetiteControl site dorsalPrimary food motivationA2A receptor stimulationMuscarinic antagonist scopolamineDA D2 antagonistsAction of pilocarpineAdenosine A2A receptorsAdenosine A2A antagonistsEffects of drugsEffort-related choiceFood-seeking behaviorSites dorsalChow intakeDA depletionDA transmissionMuscarinic receptorsD2 antagonist
2012
Dopaminergic Modulation of Effort-Related Choice Behavior as Assessed by a Progressive Ratio Chow Feeding Choice Task: Pharmacological Studies and the Role of Individual Differences
Randall P, Pardo M, Nunes E, Cruz L, Vemuri V, Makriyannis A, Baqi Y, Müller C, Correa M, Salamone J. Dopaminergic Modulation of Effort-Related Choice Behavior as Assessed by a Progressive Ratio Chow Feeding Choice Task: Pharmacological Studies and the Role of Individual Differences. PLOS ONE 2012, 7: e47934. PMID: 23110135, PMCID: PMC3478264, DOI: 10.1371/journal.pone.0047934.Peer-Reviewed Original ResearchMeSH Keywords3,3'-DiaminobenzidineAdenosine A2 Receptor AntagonistsAnalysis of VarianceAnimal FeedAnimal Nutritional Physiological PhenomenaAnimalsChoice BehaviorDopamineDopamine and cAMP-Regulated Phosphoprotein 32Dopamine AntagonistsFeeding BehaviorHaloperidolImmunohistochemistryIndividualityMalePiperidinesPyrazolesRatsRats, Sprague-DawleyXanthinesConceptsProgressive ratioLever pressesPrimary food motivationNucleus accumbens coreCB1 inverse agonistsFood-seeking behaviorChow intakeMSX-3DA transmissionDA antagonismDopaminergic modulationDrug treatmentHigh respondersLaboratory chowLow respondersChow consumptionEffort-related processesSignal transduction activityAccumbens coreMesolimbic dopaminePharmacological studiesFood-reinforced tasksInverse agonistBehavioral activationFood motivationThe Role of Adenosine in the Ventral Striatal Circuits Regulating Behavioral Activation and Effort-Related Decision Making: Importance for Normal and Pathological Aspects of Motivation
Salamone J, Correa M, Randall P, Nunes E, Pardo M, Lopez-Cruz L. The Role of Adenosine in the Ventral Striatal Circuits Regulating Behavioral Activation and Effort-Related Decision Making: Importance for Normal and Pathological Aspects of Motivation. 2012, 493-512. DOI: 10.1007/978-1-4614-3903-5_23.Peer-Reviewed Original ResearchIntra-accumbens injectionsDA depletionReceptor antagonistAccumbens DA depletionsEffort-related processesAdenosine A2A receptor antagonistA1 receptor antagonistAdenosine A2A agonistDA D2 antagonistsA2A receptor antagonistsRole of adenosineAdenosine A2A receptorsEffort-related decision makingEffort-related choice behaviorBrain dopamineNeuromodulator adenosineD2 antagonistD2 antagonismA2A agonistNucleus accumbensStriatal circuitsTendency of ratsMotivational symptomsA2A receptorsPathological aspectsThe novel adenosine A2A antagonist prodrug MSX-4 is effective in animal models related to motivational and motor functions
Santerre J, Nunes E, Kovner R, Leser C, Randall P, Collins-Praino L, Cruz L, Correa M, Baqi Y, Müller C, Salamone J. The novel adenosine A2A antagonist prodrug MSX-4 is effective in animal models related to motivational and motor functions. Pharmacology Biochemistry And Behavior 2012, 102: 477-487. PMID: 22705392, DOI: 10.1016/j.pbb.2012.06.009.Peer-Reviewed Original ResearchConceptsMSX-3Amino acid ester prodrugsTreatment of depressionDorsal striatal functionDopamine D2 receptorsSame dose rangeNucleus accumbens coreEffort-related choice behaviorConcurrent leverOral tremorD2 antagonistIntraperitoneal administrationActive dosesLocomotor suppressionMotor functionStriatal functionD2 receptorsAnxiogenic effectsMotor impairmentSelective adenosineAnimal modelsMotivational symptomsAccumbens coreAntiparkinsonian profileEster prodrugsTHE BEHAVIORAL PHARMACOLOGY OF EFFORT‐RELATED CHOICE BEHAVIOR: DOPAMINE, ADENOSINE AND BEYOND
Salamone J, Correa M, Nunes E, Randall P, Pardo M. THE BEHAVIORAL PHARMACOLOGY OF EFFORT‐RELATED CHOICE BEHAVIOR: DOPAMINE, ADENOSINE AND BEYOND. Journal Of The Experimental Analysis Of Behavior 2012, 97: 125-146. PMID: 22287808, PMCID: PMC3266736, DOI: 10.1901/jeab.2012.97-125.Peer-Reviewed Original ResearchConceptsEffort-related choice behaviorDA depletionAccumbens DA depletionsNucleus accumbens DAAccumbens DAFood-reinforced behaviorDA transmissionMesolimbic DAPsychomotor slowingEffort-related functionsNeurological disordersFood-reinforced tasksBrain structuresDrug abuseAccumbens DA transmissionBehavioral pharmacologyHigh response requirementsRatsBrain systemsPresent reviewPrimary reinforcerAntagonism
2011
Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists
Randall P, Nunes E, Janniere S, Stopper C, Farrar A, Sager T, Baqi Y, Hockemeyer J, Müller C, Salamone J. Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists. Psychopharmacology 2011, 216: 173-186. PMID: 21347642, PMCID: PMC3522121, DOI: 10.1007/s00213-011-2198-3.Peer-Reviewed Original Research
2010
The novel cannabinoid CB1 antagonist AM6545 suppresses food intake and food-reinforced behavior
Randall P, Vemuri V, Segovia K, Torres E, Hosmer S, Nunes E, Santerre J, Makriyannis A, Salamone J. The novel cannabinoid CB1 antagonist AM6545 suppresses food intake and food-reinforced behavior. Pharmacology Biochemistry And Behavior 2010, 97: 179-184. PMID: 20713079, PMCID: PMC3522179, DOI: 10.1016/j.pbb.2010.07.021.Peer-Reviewed Original ResearchConceptsAppetite suppressant drugsFood-motivated behaviorHigh-fat dietCentral nervous systemFood-reinforced behaviorSame dose rangeCB1 inverse agonistsUndesirable side effectsChow intakeIntraperitoneal administrationAM6545CB1 receptorsAppetite suppressantsCannabinoid antagonistFood intakeHigh doseSide effectsNervous systemPoor penetrabilityInverse agonistNeutral antagonistsDose rangeMild suppressionIntakeAntagonist