2023
Ventral 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 ResearchMeSH KeywordsAcetylcholineAnimalsDopamineFemaleMaleNucleus AccumbensPhysostigmineRatsRats, Sprague-DawleyReceptor, Muscarinic M5Ventral Tegmental AreaConceptsNucleus 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 ResearchMeSH KeywordsCalcium Channel BlockersCalcium Channels, L-TypeDopamineHumansMood DisordersMorbidityNucleus AccumbensSubstance-Related DisordersVentral Tegmental AreaConceptsL-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 activity
2020
Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats
Nunes EJ, Rupprecht LE, Foster DJ, Lindsley CW, Conn PJ, Addy NA. Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats. Neuropharmacology 2020, 171: 108089. PMID: 32268153, PMCID: PMC7313677, DOI: 10.1016/j.neuropharm.2020.108089.Peer-Reviewed Original ResearchConceptsSucrose preference testVentral tegmental areaMuscarinic M5 receptorsCholinergic toneM5 receptorsBehavioral effectsFemale ratsDepressive-like behavioral effectsIntra-VTA infusionAnxiogenic-like effectsAcetylcholinesterase inhibitor physostigmineAnxiety-related behaviorVTA administrationCholinergic modulationCholinergic receptorsMuscarinic receptorsInhibitor physostigmineSwim testTegmental areaMale ratsMood disordersVTA infusionsFST behaviorRatsPhysostigmine
2019
Cholinergic Receptor Blockade in the VTA Attenuates Cue-Induced Cocaine-Seeking and Reverses the Anxiogenic Effects of Forced Abstinence
Nunes EJ, Bitner L, Hughley SM, Small KM, Walton SN, Rupprecht LE, Addy NA. Cholinergic Receptor Blockade in the VTA Attenuates Cue-Induced Cocaine-Seeking and Reverses the Anxiogenic Effects of Forced Abstinence. Neuroscience 2019, 413: 252-263. PMID: 31271832, PMCID: PMC6661179, DOI: 10.1016/j.neuroscience.2019.06.028.Peer-Reviewed Original ResearchConceptsCue-induced cocaineAnxiety-related behaviorDrug relapseOpen arm timeCholinergic receptor blockadeCocaine abstinenceVentral tegmental areaSubstance abuseSelf-administer intravenous cocaineMuscarinic receptor antagonist scopolaminePeriod of abstinenceAnxiogenic effectsReceptor blockadeCholinergic mechanismsCocaine-naïve ratsNicotinic acetylcholine receptor antagonist mecamylamineMale Sprague-Dawley ratsDrug abstinenceSprague-Dawley ratsDose-dependent increaseCocaine-naive ratsAntagonist scopolamineEPM behaviorSaline ratsAbstinence
2018
The L-type calcium channel blocker, isradipine, attenuates cue-induced cocaine-seeking by enhancing dopaminergic activity in the ventral tegmental area to nucleus accumbens pathway
Addy NA, Nunes EJ, Hughley SM, Small KM, Baracz SJ, Haight JL, Rajadhyaksha AM. The L-type calcium channel blocker, isradipine, attenuates cue-induced cocaine-seeking by enhancing dopaminergic activity in the ventral tegmental area to nucleus accumbens pathway. Neuropsychopharmacology 2018, 43: 2361-2372. PMID: 29773910, PMCID: PMC6180103, DOI: 10.1038/s41386-018-0080-2.Peer-Reviewed Original ResearchConceptsL-type calcium channelsCocaine relapseLever depressionVentral tegmental areaCocaine self-administration trainingOriginal training contextLight cue presentationSelf-administration trainingSubjective effectsCocaine-seeking behaviorTegmental areaBehavioral effectsCocaine's subjective effectsL-type calcium channel blockerCue presentationMale Sprague-Dawley ratsTraining contextCocaine cuesNucleus accumbens coreNatural rewardsDA receptor activationCalcium channel blockersSprague-Dawley ratsPhasic dopaminePotential therapeutic target
2017
Enhancing VTA Cav1.3 L-type Ca2+ channel activity promotes cocaine and mood-related behaviors via overlapping AMPA receptor mechanisms in the nucleus accumbens
Martínez-Rivera A, Hao J, Tropea TF, Giordano TP, Kosovsky M, Rice RC, Lee A, Huganir RL, Striessnig J, Addy NA, Han S, Rajadhyaksha AM. Enhancing VTA Cav1.3 L-type Ca2+ channel activity promotes cocaine and mood-related behaviors via overlapping AMPA receptor mechanisms in the nucleus accumbens. Molecular Psychiatry 2017, 22: 1735-1745. PMID: 28194001, PMCID: PMC5555837, DOI: 10.1038/mp.2017.9.Peer-Reviewed Original ResearchMeSH KeywordsAffectAnimalsCalcium Channels, L-TypeCocaineCocaine-Related DisordersConditioning, PsychologicalDepressionDisease Models, AnimalDopamine Uptake InhibitorsGenetic Association StudiesHumansMaleMice, Inbred C57BLMice, TransgenicMotor ActivityNucleus AccumbensPost-Synaptic DensityReceptors, AMPASocial BehaviorVentral Tegmental AreaConceptsDepressive-like behaviorCav1.3 L-type Ca2L-type Ca2Receptor mechanismsCalcium-permeable α-aminoCACNA1D geneCav1.3 channelsRole of Cav1.3Depressive-like phenotypeMood-related behaviorsDepression-related phenotypesSocial behavioral deficitsNeuropsychiatric symptomsBehavioral deficitsMood disordersCP-AMPARNAc shellRodent studiesGluA1 phosphorylationHuman studiesNAc corePlace preferenceBipolar disorderPsychomotor activityCav1.3
2010
Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats
Addy N, Daberkow D, Ford J, Garris P, Wightman R. Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats. Journal Of Neurophysiology 2010, 104: 922-931. PMID: 20554845, PMCID: PMC2934942, DOI: 10.1152/jn.00413.2010.Peer-Reviewed Original ResearchConceptsAcute cocaine challengeCocaine challengeNucleus accumbens coreWithdrawal periodDopamine sensitizationShort withdrawal periodDopamine releaseDopamine neurotransmissionFast-scan cyclic voltammetryAccumbens coreMale Sprague-Dawley ratsSubsequent cocaine challengeSprague-Dawley ratsLonger withdrawal periodsCocaine-treated subjectsPre-exposed subjectsRepeated CocaineDaily injectionsAcute cocaineDopaminergic responseCocaine exposureDopamine overflowNAc coreDopamine uptakeUptake inhibition