The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors
Abstract
Worldwide, 100 million people are expected to die this century from the consequences of nicotine addiction, but nicotine is also known to enhance cognitive performance. Identifying the molecular mechanisms involved in nicotine reinforcement and cognition is a priority and requires the development of new in vivo experimental paradigms. The ventral tegmental area (VTA) of the midbrain is thought to mediate the reinforcement properties of many drugs of abuse. Here we specifically re-expressed the beta2-subunit of the nicotinic acetylcholine receptor (nAChR) by stereotaxically injecting a lentiviral vector into the VTA of mice carrying beta2-subunit deletions. We demonstrate the efficient re-expression of electrophysiologically responsive, ligand-binding nicotinic acetylcholine receptors in dopamine-containing neurons of the VTA, together with the recovery of nicotine-elicited dopamine release and nicotine self-administration. We also quantified exploratory behaviours of the mice, and showed that beta2-subunit re-expression restored slow exploratory behaviour (a measure of cognitive function) to wild-type levels, but did not affect fast navigation behaviour. We thus demonstrate the sufficient role of the VTA in both nicotine reinforcement and endogenous cholinergic regulation of cognitive functions.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Selective viral reexpression of β2 Ã (Maskos et al. 2005;Pons et al. 2008) or α4 Ã nAChRs in the VTA is sufficient to support both intra-VTA (Maskos et al. 2005) and systemic nicotine self-administration (Pons et al. 2008), identifying the nAChR subtypes necessary for nicotine reinforcement, as well as showing the importance of nAChRs within the VTA itself for this behavior.”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Maskos et al. 2005
In the citing paper
“ACh provides a complex regulation of reward and motivation behaviors through its actions on dopamine (DA) circuitry [68–72].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [72]
In the citing paper
“Nicotine in adolescence is thus poised to alter DA development, as it acts directly on VTA DA neurons through their expression of nAChRs, modulating their firing rate in a population-specific manner in adult rodents [72, 137–139].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [72]
In the citing paper
“Evidence for this idea stemmed from studies showing that mice lacking the ␣4, ␣6, and/or 2 nAChR subunits fail to self-administer nicotine, whereas re-expression of these subunits in the ventral tegmental area of knockout mice restored nicotine self-administration”
From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as Maskos et al., 2005
In the citing paper
“extensive studies showing that 2, ␣4, or ␣6 nAChRs knockout mice fail to self-administer nicotine (Picciotto et al., 1998;Marubio et al., 2003;Maskos et al., 2005;Pons et al., 2008).”
From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as Maskos et al., 2005
In the citing paper
“particularly because the addictive effects of nicotine are mediated primarily through stimulation of nAChRs in the VTA (Drenan et al., 2008; Maskos et al., 2005; McGranahan et al., 2011; Picciotto et al., 1998).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Maskos et al., 2005
In the citing paper
“Mice learn to run on a Y-maze to self-administer nicotine into the VTA, an effect that can be diminished by systemic administration of dopamine antagonists”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Maskos et al., 2005
In the citing paper
“Nicotine reinforcement and reward is mediated through nAChRs in the mesolimbic system (Maskos et al., 2005; McGranahan et al., 2011; Tolu et al., 2012)”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Maskos et al., 2005
Citations
Cites
A neural substrate of prediction and reward
Schultz, W., Dayan, P., & Montague, P. R. (1997) · Science · doi:10.1126/science.275.5306.1593 · Cited by 9,388
In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Naldini, L., Blömer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., Verma, I. M., & Trono, D. (1996) · Science · doi:10.1126/science.272.5259.263 · Cited by 4,903
Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6)
Mesulam, M. M., Mufson, E. J., Wainer, B. H., & Levey, A. I. (1983) · Neuroscience · doi:10.1016/0306-4522(83)90108-2 · Cited by 2,329
Swanson, L. W. (1982) · Brain Research Bulletin · doi:10.1016/0361-9230(82)90145-9 · Cited by 1,718
A neuronal model of a global workspace in effortful cognitive tasks
Dehaene, S., Kerszberg, M., & Changeux, J.-P. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.24.14529 · Cited by 1,347
Picciotto, M. R., Zoli, M., Rimondini, R., Léna, C., Marubio, L. M., Pich, E. M., Fuxe, K., & Changeux, J.-P. (1998) · Nature · doi:10.1038/34413 · Cited by 1,320
Self-citationEffects of nicotine on the nucleus accumbens and similarity to those of addictive drugs.
Pontieri, F. E., Tanda, G., Orzi, F., & Chiara, G. D. (1996) · Nature · doi:10.1038/382255a0 · Cited by 1,073
Physiological Diversity of Nicotinic Acetylcholine Receptors Expressed by Vertebrate Neurons
McGehee, D. S., & Role, L. W. (1995) · Annual Review of Physiology · doi:10.1146/annurev.ph.57.030195.002513 · Cited by 1,022
Grace, A. A., & Bunney, B. S. (1983) · Neuroscience · doi:10.1016/0306-4522(83)90135-5 · Cited by 937
Nicotinic Receptors at the Amino Acid Level
Corringer, P., Novère, N. G. L., & Changeux, J. (2000) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.40.1.431 · Cited by 832
Cited by
Sorted by citations
Items 501–568 of 568
Functional Modulation of the Mouse Prefrontal Cortex by Nicotinic Acetylcholine Receptors
Couey, J. J. (2009) · Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam)
Rotella, D. P. (2010) · Wiley eBooks · doi:10.1002/0471266949.bmc200
MacLaren, D. A. A. (2012) · St Andrews Research Repository (St Andrews Research Repository)
Hendrickson, L. M. (2011) · PubMed · doi:10.13028/174w-zb21
“The sufficiency of highaffinity, α4β2* nAChRs in mediating the rewarding properties of nicotine was further validated with the Leu9′Ala α4 knock-in nAChR mouse model (Tapper et al., 2004) as well as targeted re-expression of the β2 subunit in β2 KO mice (Maskos et al., 2005).”
BackgroundHaller, G. E. (2013) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7h70ctm
Molecular determinants of the β4 nAChR subunit in channel function and nicotine-mediated behavior
Ślimak, M. A. (2012) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-6654
Gut, N. K. (2014) · St Andrews Research Repository (St Andrews Research Repository)
A role for neuronal nicotinic receptors in ADHD like behaviors
Granon, S., Avale, M. E., Pons, S., Changeux, J., Fauré, P., & Maskos, U. (2009) · Neuroscience Research · doi:10.1016/j.neures.2009.09.1599
Pharmacological profile and clinical findings of varenicline tartrate (Champix® tablets)
Hizue, M., Ishibashi, T., & Nomura, S. (2010) · Folia Pharmacologica Japonica · doi:10.1254/fpj.135.194
Strategies for smoking cessation
Tindle, H. A. (2007) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-007-0060-2
Pons, S., Fattore, L., Cossu, G., Tolu, S., Porcu, E., McIntosh, J. M., Changeux, J., & Maskos, U. (2008)
Drenan, R. M., Patzlaff, N. E., & MichaelMcIntosh, J. (2010)
Abbreviated title: Differential brain transcriptome of 4-/- mice
Kedmi, M., & Orr‐Urtreger, A. (2006)
Dynamics and function of nicotinic acetylcholine receptors in the nervous system
Fernandes, C. D. C. (2011) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Treatment of Nicotine Dependence
Foll, B. L. (2006) · CRC Press eBooks · doi:10.1201/9781420005431.ch21
Steiner, R. C., & Picciotto, M. R. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781107360556.025
Animal Models of Nicotine Addiction
Steiner, R. C., & Picciotto, M. R. (2006) · CRC Press eBooks · doi:10.1201/9781420005431.ch3
Nicotine dependence and treatment
López‐Ibor, M. (2012) · doi:10.1093/med/9780199696758.003.0069
Schindler, A. G. (2012) · ResearchWorks at the University of Washington (University of Washington)
Relaciones en la adicción al alcohol y al tabaco. Bases neurales
Vivas-Fernández, M. (2016)
Gugusheff, J. (2015) · Adelaide Research & Scholarship (AR&S) (University of Adelaide)
The Interaction Between Genetics and Tobacco Consumption in Light Smokers
Zhu, Z. (2014) · TSpace (University of Toronto)
Olanbiwonnu, T. (2016) · TSpace (University of Toronto)
Insular Cortex Damage from Stroke and Disruption of Nicotine Dependence: The MINDS Study
Abdolahi, A. (2015) · UR Research (University of Rochester)
Ng, G. (2015) · TSpace (University of Toronto)
Staios, G. (2011) · TSpace (University of Toronto)
Tobacco Smoking, Food Intake, and Weight Control
Li, M. D. (2018) · Springer eBooks · doi:10.1007/978-981-10-7530-8_15
Pharmacological Basis of the Clinical Efficacy of Varenicline Used to Facilitate Smoking Cessation
Gilyarevskiy, S. R. (2019) · Rational Pharmacotherapy in Cardiology · doi:10.20996/1819-6446-2019-15-1-95-104
Ethyl-for-methyl substitution enhances the subtype specificity of mecamylamine analogues
Mangan, D. P., McNabola, N., Clark, E. H., Bermúdez, I., Wonnacott, S., & Southern, J. M. (2019) · Organic & Biomolecular Chemistry · doi:10.1039/c9ob01993f
Nicotine exposure and neuronal activity regulate Golgi membrane dispersal and distributionPreprint
Govind, A. P., Jeyifous, O., Russell, T. A., Vaasjo, L. O., Yi, Z., Weigel, A. V., Newell, L. P., Koranda, J. L., Singh, K. V., Valbuena, F. M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.25.965285
Hoang, M. (2020) · TSpace (University of Toronto)
Sugar consumption and expression of neuronal nicotinic receptors in the Nucleus Accumbens
Ali, S. A. (2021) · Queensland University of Technology · doi:10.5204/thesis.eprints.208972
Berridge, K. C. (2014) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718235070.793489919
Grunberg, N. E. (2011) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.11827959.12926057
A Biological/Genetic Perspective: The Addicted Brain
Kelly, T. H., Harvanko, A. M., Pierce, M. E., Rayapati, A. O., & Martin, C. A. (2018) · Issues in children's and families' lives · doi:10.1007/978-3-319-90611-9_3
Substance dependence and abuse
Pietropaolo, S., Sluyter, F., & Crusio, W. E. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781107360556.024
The Pharmacist's Role in Smoking Cessation
Wick, J. Y. (2008) · The Consultant Pharmacist · doi:10.4140/tcp.n.2008.68
Nicotine in adolescence freezes dopamine circuits in an immature statePreprint
Reynolds, L. M., Gulmez, A., Fayad, S. L., Campos, R. C., Rigoni, D., Nguyen, C., Borgne, T. L., Topilko, T., Rajot, D., Franco, C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.28.564518
Fayad, S., Reynolds, L. M., Torquet, N., Tolu, S., Mondoloni, S., Nguyen, C., Justo, R., Didienne, S., Debray, N., Viollet, C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.28.564522
Nicotinic Acetylcholine Receptors, Cannabinoid Receptors, and Their Interplay in Drug Addiction
Vallés, A. S., & Barrantes, F. J. (2024) · Springer eBooks · doi:10.1007/978-3-031-72219-6_24
Xu, W., Wang, M., Li, X., He, R., Ding, R., Bao, J., Zhangsun, D., & Luo, S. (2025) · Marine Drugs · doi:10.3390/md23030109
“Genetic deletion studies demonstrate α 4 [39,41]/ α 6 [22,24] and β 2 [39,42] subunits critically regulate nicotine-seeking behaviors.”
Exploration and behavioral variability
Fauré, P. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-29867-7.00026-8 · Cited by 1
Dopamine modulation of synaptic transmission in drug addiction
Reva, M., & Lüscher, C. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-29867-7.00037-2
Yang, X., Li, S., Liu, J., Hou, L., Liu, R., Sun, X., Yao, R., Wang, M., Wu, F., Yu, P., et al. (2025) · Angewandte Chemie · doi:10.1002/ange.202506692
A Cre‐dependent lentiviral vector for neuron subtype‐specific expression of large proteins
Xue, W., Picaud, S., Hepp, R., Pons, S., Maskos, U., Lambolez, B., & Tricoire, L. (2025) · FEBS Letters · doi:10.1002/1873-3468.70205
“…was performed in Stbl3 bacteria (Life Technologies, Villebon sur Yvette, France) grown at 37 ° C for up to 12 h. Recombinant lenti pseudo-virions were produced as described [19] and titers of viral suspensions determined by qPCR on HCT116 cells: 9.4 9 10 8 infectious genomes (IG) (cid:1) mL (cid”
InfluentialArib, O. (2009) · theses.fr (ABES) · doi:10.70675/b585acc3z0d1cz4458zb20azdc445f0b7743
“Les sous-unités ß2 auraient aussi un rôle dans les fonctions cognitives (Besson et al, 2008), et plus particulièrement les ß2 situés dans l’aire tegmentale ventrale (Maskos et al, 2005 ; Molles et al, 2006), et dans les réactions de peur conditionnée (Davis et Gould, 2007).”
BackgroundThe role of β4-containing nicotinic acetylcholine receptors in nicotine addiction
Harrington, L. (2015) · theses.fr (ABES) · doi:10.70675/835afebdzb53ez461ez920cz1f4b0acd17a6
Hay, Y. A. (2014) · theses.fr (ABES) · doi:10.70675/e05a8175zd583z4b2ezbb03ze7d3e536abc3
Rôle du transporteur plasmique des monoamines (PMAT) dans le système nerveux central
Amin, S. R. (2017) · theses.fr (ABES) · doi:10.70675/f562837bz937fz402eza824z24af264eaf90
Rôle des stimuli sensoriels et de la palatabilité dans la prise orale de nicotine chez la souris
Tannous, S. (2019) · theses.fr (ABES) · doi:10.70675/eaa3d755ze7a1z4017z893dz1b7fd3cd4d8d
Diversité des effets de la nicotine sur les neurones dopaminergiques de l’aire tegmentale ventrale
Nguyen, C. (2020) · theses.fr (ABES) · doi:10.70675/57dc4740z36f1z4ee7z87e7z960af8c4a43e
Dynamiques dopaminergiques dans la prise de décision : rôle dans la variabilité et l’exploration
Côme, M. (2023) · theses.fr (ABES) · doi:10.70675/a7b03d10z7e3cz45a1z817bza6c6344893af
Singh, A., Verma, N., Kant, S., Verma, A. K., Tripathi, A., & Bhardwaj, K. (2026) · Journal of the Association of Physicians of India · doi:10.59556/japi.74.1471
From Genes to Behavior: Mouse Models of the Cholinergic System
Lamprou, E., Kolydas, N., & Konsolaki, E. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1015550
Janíčková, H., Abbondanza, A., Eliáš, J., Verma, C., Barboza, A., Čapek, M., Dhabalia, T., Grígelová, A., Dumas, S., & Bernard, V. (2026) · Research Square · doi:10.21203/rs.3.rs-10142145/v1
Focal drug uncaging for the precise control of endogenous nicotinic receptors in behaving micePreprint
Guyon, N., Mohayyaei, M., Bergel, A., Grellier, G., Jehl, J., Pietrancosta, N., Rebola, N., François, A., Fauré, P., Ellis‐Davies, G. C. R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.02.755724
BindingDB (2014) · UC San Diego · doi:10.7270/q2jw8gbv
Regulation and Function of Neuronal Nicotinic Acetylcholine Receptors in Lung Cancer: A Dissertation
Improgo, M. R. (2011) · eScholarship@UMassChan · doi:10.13028/2t06-nc13
“accumbens [87-90].”
Kota, D. (2008) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/ps6p-8s62
“In addition, targeted expression of β2 subunits in the VTA of β2knockout mice reinstates nicotine-induced DA release (Maskos et al. 2005).”
Background
Metadata
- Authors
- Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J.-P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., Dufour, N., Cloëz-Tayarani, I., Bemelmans, A.-P., Mallet, J., Gardier, A. M., David, V., Faure, P., Granon, S., & Changeux, J.-P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université Paris-Sud (FR)
- Corresponding author
- Changeux, J.-P.
- ORCID
- Venue
- Nature
- Published
- 2005-07
- Volume
- 436
- Issue
- 7047
- Pages
- 103-107
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2141456252
- Cited by
- 566
- References
- 32
- Citations by year
- 2026: 7 · 2025: 19 · 2024: 7 · 2023: 18 · 2022: 10 · 2021: 18 · 2020: 21 · 2019: 17 · 2018: 21 · 2017: 17 · 2016: 15 · 2015: 26 · 2014: 32 · 2013: 34 · 2012: 32
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine, nicotinic acetylcholine receptors, beta2 subunit, ventral tegmental area, dopaminergic neurons, nicotine self-administration, nicotine reinforcement, nicotine dependence, cognitive function, exploratory behavior, lentiviral vectors, cholinergic modulation, dopamine release
- MeSH terms
- Animals, Cognition, Dopamine, Exploratory Behavior, Locomotion, Morphine, Neurons, Nicotine, Receptors, Nicotinic, Gene Expression, Ventral Tegmental Area, Receptors, Adrenergic, beta-2, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
