Nii Addy, PhD
Research & Publications
Biography
News
Research Summary
Our research examines the neurobiological mechanisms of reinforcement learning and motivational control and seeks to identify how these mechanisms are altered in psychiatric illnesses. We are currently investigating the neurobiological processes that underlie the ability of drugs of abuse, reward-associated cues, or ongoing stressors to modulate behavior. In this work, we use an integrative methodological approach that incorporates in vivo electrochemistry (fast scan cyclic voltammetry), rodent behavioral models, cellular and molecular tools, and newly incorporated electrophysiology tools to examine the role of cholinergic, dopaminergic and L-type calcium channel (LTCC) mechanisms in substance use disorders (SUD), mood disorders, and comorbid SUDs and mood disorders.
Our findings show that midbrain cholinergic and LTCC mechanisms powerfully regulate cue-induced drug-seeking behavior and mood disorder-related behavioral phenotypes. Further, our work suggests that LTCCs and cholinergic receptors may serve as potential therapeutic targets for SUDs and mood disorders, like major depressive disorder (MDD). In other work, we are also examining the ability of tobacco product flavor constituents to alter nicotine reward, nicotine aversion, nicotine choice and taking behavior, and nicotine reinforcement through regulation of phasic dopamine signaling. The goals of our research are to provide new insight into the mechanistic bases of complex behaviors associated with psychiatric illness, to inform FDA policy decisions regarding the regulation of flavor constituents in tobacco products, and to identify novel therapeutic targets to treat psychiatric disorders,
Specialized terms: Neurobiology of addiction; In vivo electrochemistry; Behavioral pharmacology; Systems neuroscience; Neurotransmission; Signal transduction
Coauthors
Research Interests
Behavioral Sciences; Electrochemistry; Neurobiology; Psychiatry; Signal Transduction; Substance-Related Disorders
Selected Publications
- Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric DisordersNunes 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.
- Ventral tegmental area M5 muscarinic receptors mediate effort-choice responding and nucleus accumbens dopamine in a sex-specific mannerNunes 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.
- Chapter 11 Cholinergic modulation of circuitsAddy N, Fowler C, Wickham R. Chapter 11 Cholinergic modulation of circuits. 2023, 409-444. DOI: 10.1016/b978-0-12-823453-2.00004-7.
- Chronic oral nicotine exposure decreases aversive taste of nicotine, increases nicotine withdrawal and reinstatement, but cherry flavor does not alter nicotine’s effects in adolescent ratsBagdas D, Harris L, Addy N. Chronic oral nicotine exposure decreases aversive taste of nicotine, increases nicotine withdrawal and reinstatement, but cherry flavor does not alter nicotine’s effects in adolescent rats. Neuroscience Letters 2022, 793: 137008. PMID: 36476758, PMCID: PMC9948648, DOI: 10.1016/j.neulet.2022.137008.
- 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-morbiditiesNunes 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, DOI: 10.1016/j.neuropharm.2022.109336.
- Cholinergic and dopaminergic‐mediated motivated behavior in healthy states and in substance use and mood disordersNunes 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.
- Animal Models to Investigate the Impact of Flavors on Nicotine Addiction and DependenceBagdas D, Kebede N, Zepei AM, Harris L, Minanov K, Picciotto MR, Addy NA. Animal Models to Investigate the Impact of Flavors on Nicotine Addiction and Dependence. Current Neuropharmacology 2022, 20: 2175-2201. PMID: 35611777, PMCID: PMC9886843, DOI: 10.2174/1570159x20666220524120231.
- Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry (CIS-FSCV) to Assess Ventral Tegmental Area Receptor Regulation of Phasic DopamineWickham R, Lehr M, Mitchell L, Addy N. Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry (CIS-FSCV) to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine. Journal Of Visualized Experiments 2020 DOI: 10.3791/60886-v.
- Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in ratsNunes 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.
- Cholinergic Receptor Blockade in the VTA Attenuates Cue-Induced Cocaine-Seeking and Reverses the Anxiogenic Effects of Forced AbstinenceNunes 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.
- The L-type calcium channel blocker, isradipine, attenuates cue-induced cocaine-seeking by enhancing dopaminergic activity in the ventral tegmental area to nucleus accumbens pathwayAddy 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.
- Evaluating oral flavorant effects on nicotine self-administration behavior and phasic dopamine signalingWickham RJ, Nunes EJ, Hughley S, Silva P, Walton SN, Park J, Addy NA. Evaluating oral flavorant effects on nicotine self-administration behavior and phasic dopamine signaling. Neuropharmacology 2017, 128: 33-42. PMID: 28943284, PMCID: PMC5714675, DOI: 10.1016/j.neuropharm.2017.09.029.
- Enhancing VTA Cav1.3 L-type Ca2+ channel activity promotes cocaine and mood-related behaviors via overlapping AMPA receptor mechanisms in the nucleus accumbensMartínez-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.
- Chapter 38 Clinical Syndromes of Substance Use DisorderAddy N, Solecki W. Chapter 38 Clinical Syndromes of Substance Use Disorder. 2016, 619-634. DOI: 10.1016/b978-0-12-800105-9.00038-x.
- Examination of Rapid Dopamine Dynamics with Fast Scan Cyclic Voltammetry During Intra-oral Tastant Administration in Awake RatsWickham 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.
- Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in RatsAddy 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.
- S43 INVOLVEMENT OF SIGNAL TRANSDUCTION CASCADES IN NICOTINE REINFORCEMENTPicciotto M, Fornaserio E, Addy N, Brunzell D. S43 INVOLVEMENT OF SIGNAL TRANSDUCTION CASCADES IN NICOTINE REINFORCEMENT. Behavioural Pharmacology 2005, 16: s14. DOI: 10.1097/00008877-200509001-00043.
- Hippocampal α7 and α4β2 nicotinic receptors and working memoryLevin E, Bradley A, Addy N, Sigurani N. Hippocampal α7 and α4β2 nicotinic receptors and working memory. Neuroscience 2002, 109: 757-765. PMID: 11927157, DOI: 10.1016/s0306-4522(01)00538-3.
- Persistent behavioral consequences of neonatal chlorpyrifos exposure in ratsLevin E, Addy N, Nakajima A, Christopher N, Seidler F, Slotkin T. Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats. Brain Research 2001, 130: 83-89. PMID: 11557096, DOI: 10.1016/s0165-3806(01)00215-2.