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 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 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