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
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–300 of 568
Direct effect of nicotine on mesolimbic dopamine release in rat nucleus accumbens shell
Kleijn, J., Folgering, J. H. A., van der Hart, M. C. G., Rollema, H., Cremers, T. I. F. H., & Westerink, B. H. C. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.02.035 · Cited by 50
Coppola, J. J., & Disney, A. A. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00008 · Cited by 48
“…been associated with a range of cognitive processes including learning and memory consolidation (Hasselmo and McGaughy, 2004), reward and addiction (Maskos et al., 2005; Kobayashi and Okada, 2007; Chubykin et al., 2013), plasticity (Bear and Singer, 1986; Weinberger, 2003), the sleep/wake cycle…”
BackgroundIn SilicoModels for the Human α4β2 Nicotinic Acetylcholine Receptor
Haddadian, E. J., Cheng, M. H., Coalson, R. D., Xu, Y., & Tang, P. S. (2008) · The Journal of Physical Chemistry B · doi:10.1021/jp804868s · Cited by 48
Attention-deficit/hyperactivity disorder: A plausible mouse model?
Granon, S., & Changeux, J. (2006) · Acta Paediatrica · doi:10.1080/08035250600719747 · Cited by 53
“Very recently, in the b2 // / mice, the b2 subunit was locally re-expressed by stereotaxic injection of a lentiviral vector within the dopaminergic ventral tegmental area (VTA) [44].”
BackgroundInfluentialAAV-Directed Persistent Expression of a Gene Encoding Anti-Nicotine Antibody for Smoking Cessation
Hicks, M. J., Rosenberg, J. B., De, B. P., Pagovich, O. E., Young, C. N., Qiu, J., Kaminsky, S. M., Hackett, N. R., Worgall, S., Janda, K. D., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003611 · Cited by 48
Rate of flow of aqueous humor determined from measurements of aqueous flare.
McLaren, J. W., Trocmé, S. D., Relf, S. J., & Brubaker, R. F. (1990) · PubMed · Cited by 47
Soma, S., Shimegi, S., Suematsu, N., Tamura, H., & Sato, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068430 · Cited by 46
“functions including sensation [1,2], attention [3–5], learning and memory [6–8], cognition [9], and regulation of the behavioral state [10].”
BackgroundNicotine and alcohol: the role of midbrain dopaminergic neurons in drug reinforcement
Morel, C., Montgomery, S. E., & Han, M. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14160 · Cited by 50
“…2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd European Journal of Neuroscience, 50, 2180–2200 viral re-expression of b2 nAChRs in both VTA DA and GABA neurons are required to restore spontaneous VTA DA neuron bursting activity (Maskos et al., 2005; Tolu et al., 2012).”
BackgroundZaniewska, M., McCreary, A. C., Przegaliński, E., & Filip, M. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.04.034 · Cited by 46
Nicotine addiction: More than just dopamine
Kim, K. K. O., & Picciotto, M. R. (2023) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2023.102797 · Cited by 46
Naber, M., Hommel, B., & Colzato, L. S. (2015) · Scientific Reports · doi:10.1038/srep13188 · Cited by 45
Exposure to chronic intermittent nicotine vapor induces nicotine dependence
George, O., Grieder, T. E., Cole, M., & Koob, G. F. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.04.013 · Cited by 45
The Role of CaMKII and ERK Signaling in Addiction
Jia, W., Kawahata, K., Cheng, A., & Fukunaga, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063189 · Cited by 44
The Role of Nicotine in Schizophrenia
Featherstone, R. E., & Siegel, S. J. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.07.002 · Cited by 47
Modulation of the Ca2+ conductance of nicotinic acetylcholine receptors by Lypd6
Darvas, M., Morsch, M., Rácz, I., Ahmadi, S., Swandulla, D., & Zimmer, A. (2009) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2009.03.007 · Cited by 46
“…nicotinic receptor function, we next evaluated behaviors that are modulated by cholinergic neurotransmission and/or nicotine administration (Champtiaux and Changeux, 2004, Dani, 2001, Marubio et al., 1999, Maskos et al., 2005, Picciotto et al., 2000, Picciotto et al., 1995, Stevens and Wear, 1997).”
Cell autonomy, receptor autonomy, and thermodynamics in nicotine receptor up-regulation
Nashmi, R., & Lester, H. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.06.040 · Cited by 43
“Activation of α4β2* nicotinic receptor subunits is necessary and sufficient for tolerance, sensitization and reward behavior [4-6].”
BackgroundOliveira, A. S. F., Ciccotti, G., Haider, S. M., & Mulholland, A. J. (2021) · The European Physical Journal B · doi:10.1140/epjb/s10051-021-00157-0 · Cited by 43
Behavioral Sequence Analysis Reveals a Novel Role for ß2* Nicotinic Receptors in Exploration
Maubourguet, N., Lesne, A., Changeux, J., Maskos, U., & Fauré, P. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000229 · Cited by 43
“Lentiviral reexpression techniques indicate that this phenotype is linked to the expression of ß2*-nAChRs in the ventral tegmental area [6,7] and in the Substantia Nigra [8].”
Exley, R., Moroni, M., Sasdelli, F., Houlihan, L. M., Lukas, R., Sher, E., Zwart, R., & Bermúdez, I. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03915.x · Cited by 42
“The a4b2 nACh receptor has been implicated in learning and memory, nociception and nicotine dependence (Picciotto et al. 2001; Tapper et al. 2004; Maskos et al. 2005).”
BackgroundFunctional alterations of nicotinic neurotransmission in dopamine transporter knock-out mice
Weiss, S., Tzavara, E. T., Davis, R. J., Nomikos, G. G., McIntosh, J. M., Giros, B., & Martres, M. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.02.002 · Cited by 44
A concurrent excitation and inhibition of dopaminergic subpopulations in response to nicotine
Eddine, R., Valverde, S., Tolu, S., Dautan, D., Hay, A., Morel, C., Cui, Y., Lambolez, B., Venance, L., Marti, F., et al. (2015) · Scientific Reports · doi:10.1038/srep08184 · Cited by 42
“Thus, while an increase in neuronal firing is the direct consequence of nAChR activation at the level of VTA DA neurons 3,15 , an inhibition of neuronal firing can only be indirectly explained by a yet-unidentified mechanism counteracting the direct excitation.”
Sweet taste potentiates the reinforcing effects of e-cigarettes
Kroemer, N. B., Veldhuizen, M. G., Delvy, R., Patel, B. P., O’Malley, S. S., & Small, D. M. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.07.102 · Cited by 279
Cholinergic modulation of response gain in the rat primary visual cortex
Soma, S., Shimegi, S., Suematsu, N., & Sato, H. (2013) · Scientific Reports · doi:10.1038/srep01138 · Cited by 42
Yoshimura, R. F., Hogenkamp, D. J., Li, W. Y., Tran, M. B., Belluzzi, J. D., Whittemore, E. R., Leslie, F. M., & Gee, K. W. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.128751 · Cited by 43
“These pharmacological studies have been more recently supported by molecular studies implicating the importance of 2- containing (Picciotto et al., 1998; Maskos et al., 2005) and 4-containing (Tapper et al., 2004) nAChRs in behavioral responding for nicotine rewards.”
BackgroundBrunzell, D. H., McIntosh, J. M., & Papke, R. L. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12421 · Cited by 43
Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice
Kotagale, N. R., Chopde, C. T., Umekar, M. J., & Taksande, B. G. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.02.033 · Cited by 41
The Endocannabinoid System: A New Molecular Target for the Treatment of Tobacco Addiction
Scherma, M., Fadda, P., Foll, B. L., Forget, B., Fratta, W., Goldberg, S. R., & Tanda, G. (2008) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152708786927859 · Cited by 43
McCallum, S. E., Parameswaran, N., Bordia, T., Fan, H., McIntosh, J. M., & Quik, M. (2006) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.104414 · Cited by 48
“This interpretation is consistent with previous work in nAChR mutant mice, suggesting that 4 2* nAChRs are important in nicotine addiction (Picciotto et al., 1998; Klink et al., 2001; Tapper et al., 2004; Maskos et al., 2005; Walters et al., 2006).”
ResultNicotinic Activation of Laterodorsal Tegmental Neurons: Implications for Addiction to Nicotine
Ishibashi, M., Leonard, C. S., & Kohlmeier, K. A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.82 · Cited by 41
“…activation of nicotinic acetylcholine receptors (nAChRs) located in the VTA is critical for nicotine addiction (Calabresi et al, 1989; Clarke, 1993; Maskos et al, 2005; Picciotto et al, 1998; Pidoplichko et al, 1997; Pons et al, 2008; Wada et al, 1989), synaptic mechanisms both upstream and…”
Anderson, S. M., & Brunzell, D. H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048665 · Cited by 41
“tration, models of nicotine reward and reinforcement [21–32] (but see [33]).”
Gallego, X., Molas, S., Amador‐Arjona, A., Marks, M. J., Robles, N., Murtra, P., Armengol, L., Fernández-Montes, R. D., Gratacòs, M., Pumarola, M. B., et al. (2011) · Amino Acids · doi:10.1007/s00726-011-1149-y · Cited by 45
Estakhr, J., Abazari, D., Frisby, K., McIntosh, J. M., & Nashmi, R. (2017) · Current Biology · doi:10.1016/j.cub.2017.05.084 · Cited by 40
Quarta, D., Naylor, C. G., Barik, J., Fernandes, C., Wonnacott, S., & Stolerman, I. P. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1281-x · Cited by 39
A versatile system for the neuronal subtype specific expression of lentiviral vectors
Tolu, S., Avale, M. E., Nakatani, H., Pons, S., Parnaudeau, S., Tronche, F., Vogt, A., Monyer, H., Vogel, R., de Chaumont, F., et al. (2009) · The FASEB Journal · doi:10.1096/fj.09-139790 · Cited by 40
“Viral production procedures have been previously described (21).”
MethodBaker, L. K., Mao, D., Chi, H., Govind, A. P., Vallejo, Y. F., Iacoviello, M., Herrera, S., Cortright, J. J., Green, W. N., McGehee, D. S., et al. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12114 · Cited by 39
Metaxas, A., Bailey, A., Barbano, M. F., Galeote, L., Maldonado, R. J., & Kitchen, I. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00246.x · Cited by 38
“Moreover, deletion of the b2 subunit gene attenuates nicotine self-administration (Picciotto et al. 1998) and its re-expression in the VTA of b2 subunit knockout animals re-establishes the behavior (Maskos et al. 2005).”
BackgroundHay, Y. A., Andjelić, S., Badr, S., & Lambolez, B. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0869-7 · Cited by 39
Repérant, C., Pons, S., Dufour, E., Rollema, H., Gardier, A. M., & Maskos, U. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.10.007 · Cited by 41
“Three groups of mice were vectorized with a lentiviral vector as previously described (Maskos et al., 2005; Mameli-Engvall et al., 2006; Pons et al., 2008): WT mice obtained an injection of the eGFP-only expressing vector, Fig.”
BackgroundMethodInfluentialMenthol and nicotine oppositely modulate body temperature in the rat
Ruskin, D. N., Anand, R., & LaHoste, G. J. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.01.006 · Cited by 39
Novel pharmacotherapeutic targets for the management of drug addiction
Heidbreder, C. A. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.09.038 · Cited by 38
Zhu, H., Lee, M.-S., Agatsuma, S., & Hiroi, N. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm027 · Cited by 39
From antipsychotic to anti-schizophrenia drugs: role of animal models
Geyer, M. A., Olivier, B., Joëls, M., & Kahn, R. S. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.06.006 · Cited by 40
Cocaine-Evoked Synaptic Plasticity of Excitatory Transmission in the Ventral Tegmental AreaPreprint
Lüscher, C. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012013 · Cited by 37
Falk, S., Petersen, J., Svendsen, C., Leguizamón, C. R. R., Jørgensen, S. H., Krauth, N., Ludwig, M. Q., Lundø, K., Roostalu, U., Skovbjerg, G., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112466 · Cited by 38
“Also, because nicotine’s effect on dopamine neurons in the VTA is considered key to the rewarding and addictive aspects of smoking, 26,31,32 another fascinating probability is that liraglutide appropriately circumvents this vice of nicotine administration.”
BackgroundAmin, S. R., Gruszczynski, C., Guiard, B. P., Callebert, J., Launay, J., Louis, F., Betancur, C., Vialou, V., & Gautron, S. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14684 · Cited by 44
Acharya, S., & Kim, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094299 · Cited by 40
Non-equivalent Ligand Selectivity of Agonist Sites in (α4β2)2α4 Nicotinic Acetylcholine Receptors
Mazzaferro, S., Gasparri, F., New, K., Alcaino, C., Faundez‐Parraguez, M., Vasquez, P. E. I., Vijayan, R., Biggin, P. C., & Bermúdez, I. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.555136 · Cited by 37
“The ( 4 2)2 4 nAChR is one of two alternate forms of the 4 2 nAChR (14), the most abundant nAChR type in the brain and a key mediator of the rewarding and reinforcing effects of nicotine (15, 16).”
BackgroundVarenicline: New treatment with efficacy in smoking cessation
Reus, V. I., Obach, R. S., Coe, J. W., Faessel, H. M., Rollema, H., Watsky, E. J., & Reeves, K. R. (2007) · Drugs of today · doi:10.1358/dot.2007.43.2.1069956 · Cited by 36
“Although nicotinic acetylcholine receptors (nAChRs) are expressed throughout the central nervous system, it has been demonstrated that nicotine stimulation of dopamine release results from direct activation of the nAChRs in the ventral tegmental area (15).”
BackgroundDevelopment of Novel Pharmacotherapeutics for Tobacco Dependence: Progress and Future Directions
Harmey, D., Griffin, P. R., & Kenny, P. J. (2012) · Nicotine & Tobacco Research · doi:10.1093/ntr/nts201 · Cited by 37
“The stimulatory effect of nicotine on midbrain dopamine transmission is considered central to its reinforcing properties that contribute to the development and maintenance of the tobacco habit (Exley et al., 2011; Maskos et al., 2005; Pons et al., 2008).”
BackgroundPaterson, N. E. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.12.009 · Cited by 37
Characterizing Ligand-Gated Ion Channel Receptors with Genetically Encoded Ca++ Sensors
Yamauchi, J. G., Nemecz, Á., Nguyen, Q. T., Muller, A., Schroeder, L. F., Talley, T. T., Lindstrom, J. M., Kleinfeld, D., & Taylor, P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016519 · Cited by 37
“For example: the a7-nAChR is targeted for schizophrenia [2], Alzheimer’s disease [3], and cognition enhancement [4], and the a4b2-nAChR is also targeted for Alzheimer’s disease [5,6], and for tobacco addiction [7,8].”
BackgroundKoukouli, F., Rooy, M., Changeux, J.-P., & Maskos, U. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1614417113 · Cited by 33
“These defects in the maturation of the cerebral cortex that have been reported in the β2 KO mice could contribute to the observed behavioral deficits (4, 13, 16).”
BackgroundSelf-citationMillar, N. S. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.06.015 · Cited by 36
“successfully to examine neuronal nAChR α4 [141], α6 [141], α7 [142], and β2 [143]”
Harrington, L., Viñals, X., Herrera-Solís, A., Flores, Á., Morel, C., Tolu, S., Fauré, P., Maldonado, R. J., Maskos, U., & Robledo, P. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.346 · Cited by 36
β2* nAChRs on VTA dopamine and GABA neurons separately mediate nicotine aversion and reward
Grieder, T. E., Besson, M., Maal‐Bared, G., Pons, S., Maskos, U., & van der Kooy, D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908724116 · Cited by 45
“nAChRs are pentameric, ligand-gated ion channels that contain various combinations of subunits, designated α2-α10 and β2-β4, that bind acetylcholine and nicotine (11).”
BackgroundInfluentialAutism - A Neurodevelopmental Journey from Genes to Behaviour
Eapen, V. (2011) · InTech eBooks · doi:10.5772/974 · Cited by 36
Chipana, C., Garcia‐Ratés, S., Camarasa, J., Pubill, D., & Escubedo, E. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.07.016 · Cited by 37
Cahir, E., Pillidge, K., Drago, J., & Lawrence, A. J. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.35 · Cited by 37
Unraveling the neurobiology of nicotine dependence using genetically engineered mice
Stoker, A. K., & Markou, A. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.02.013 · Cited by 38
“Additionally, self-administration of nicotine directly into the VTA did not occur in b2 knockout mice, whereas nicotine self-administration behavior was reinstated after lentiviral re-expression of the b2 nAChR subunit in this brain area [14].”
BackgroundResultMesolimbic Dopamine and Habenulo-Interpeduncular Pathways in Nicotine Withdrawal
Dani, J. A., & De Biasi, M. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012138 · Cited by 34
“responses (Maskos et al. 2005).”
Vanhille, N., Belin‐Rauscent, A., Mar, A. C., Ducret, E., & Belin, D. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.204 · Cited by 33
“…system which has been demonstrated to control sign-tracking (Palmatier et al, 2013), likely through its control over dopaminergic neurons (Maskos et al, 2005; Avale et al, 2008) or prefrontal function (Paolone et al, 2013), eventually resulting in a modulation of attention and reward…”
BackgroundMeydan, C., Bekenstein, U., & Soreq, H. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00189 · Cited by 34
Hu, T., Yang, Z., & Li, M. D. (2018) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-018-9800-y · Cited by 34
Coura, R. S., Cressant, A., Xia, J., de Chaumont, F., Olivo‐Marin, J. C., Pelloux, Y., Dalley, J. W., & Granon, S. (2013) · The FASEB Journal · doi:10.1096/fj.13-231084 · Cited by 33
“the 2-subunit of the nAChRs specifically into the PFC of 2 / mice was sufficient to restore normal social patterns in these animals, thus showing that 2 / social defects were not due to gross compensatory mechanisms (24, 34, 35).”
BackgroundRevisiting nicotine’s role in the ageing brain and cognitive impairment
Majdi, A., Kamari, F., Vafaee, M. S., & Sadigh‐Eteghad, S. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0008 · Cited by 35
Cellular events in nicotine addiction
Penton, R. E., & Lester, R. A. J. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.01.001 · Cited by 33
“While other CNS nuclei were affected, these data highlight particularly significant increases in α4* nAChR function in GABAergic neurons of the VTA and substantia nigra (but not in the principle dopaminergic cells), as well as in the perforant path of the hippocampus [66].”
BackgroundInfluentialRezayof, A., Darbandi, N., & Zarrindast, M. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2008.03.004 · Cited by 33
“Furthermore, several investigations showed that intra-VTA administration of nicotine improves learning processes (Maskos et al., 2005), induces conditioned place preference (Laviolette & van der Kooy, 2003; Museo & Wise, 1994) and elicits drug-seeking behavior (David, Besson, Changeux, Cranon, &…”
BackgroundNgolab, J., Liu, L., Zhao-Shea, R., Gao, G., Gardner, P. D., & Tapper, A. R. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4453-14.2015 · Cited by 35
Brunzell, D. H. (2012) · Nicotine & Tobacco Research · doi:10.1093/ntr/nts089 · Cited by 36
Changeux, J.-P. (2006) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2006.1832 · Cited by 31
From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules
Nasiripourdori, A., Taly, V., Grütter, T., & Taly, A. (2011) · Toxins · doi:10.3390/toxins3030260 · Cited by 31
“Nicotine is also important medically because it is thought to be responsible for tobacco addiction through the stimulation of nAChR on dopaminergic neurons of the ventral tegmental area (VTA) [26].”
BackgroundNicotinic receptors and nicotine addiction
Changeux, J. (2009) · Comptes Rendus Biologies · doi:10.1016/j.crvi.2009.02.005 · Cited by 34
“…steps: invalidation of the gene encoding the subunit defined, followed by quantitative analysis of the physiology and behavior of the animal; then re-expression of the gene at a critical site in the brain using a lentiviral vector developed three years ago in my laboratory by Uwe Maskos [20].”
MethodIs immunotherapy an opportunity for effective treatment of drug addiction?
Zalewska-Kaszubska, J. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.09.079 · Cited by 31
Berry, J. N., Engle, S. E., McIntosh, J. M., & Drenan, R. M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.07.052 · Cited by 32
“a4b2 nAChRs are both necessary and/or sufficient for most aspects of nicotine addiction in mouse models, including reward, self-administration, tolerance, behavioral and cellular sensitization, and enhanced firing of VTA DA neurons (Tapper et al., 2004, 2007; Maskos et al., 2005; Mameli-Engvall et al., 2006; Pons et a…”
BackgroundCholinergic Receptors and Addiction
Papke, R. L., Brunzell, D. H., & Biasi, M. D. (2020) · Current topics in behavioral neurosciences · doi:10.1007/7854_2020_139 · Cited by 30
Renda, A., & Nashmi, R. (2014) · BMC Neuroscience · doi:10.1186/1471-2202-15-89 · Cited by 33
“Self-administration of nicotine is absent in both α4 and β2 KO mice but selective re-expression of the knocked-out subunit (either α4 or β2) in the VTA of KO mice re-establishes nicotine self-administration [5,15], which forges a strong link between the activity of these subunits and nicotine dependence.”
InfluentialMaskos, U. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04224.x · Cited by 31
“WT mice exhibited a clear nicotine-seeking behaviour from the second learning session, as measured by both the increasing choice of the nicotine-reinforced arm and decreasing latency to trigger the injections over time (Maskos et al. 2005; Besson et al. 2006; David et al. 2006).”
BackgroundMethodInfluentialMineur, Y. S., Brunzell, D. H., Grady, S. R., Lindstrom, J. M., McIntosh, J. M., Marks, M. J., King, S. L., & Picciotto, M. R. (2009) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2008.00468.x · Cited by 33
Role of endogenous acetylcholine in the control of the dopaminergic system via nicotinic receptors
Maskos, U. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06798.x · Cited by 32
Hypocretin mechanisms in nicotine addiction: evidence and speculation
Corrigall, W. A. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1588-2 · Cited by 29
Xu, J., Cohen, B. N., Zhu, Y., Dziewczapolski, G., Panda, S., Lester, H. A., Heinemann, S. F., & Contractor, A. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.78 · Cited by 30
“The roles of β2* receptors in nicotine addiction has been well established, and the involvement of nAChRs in drug reinforcement pathways are well documented (9, 58).”
BackgroundDisney, A. A., Alasady, H. A., & Reynolds, J. H. (2014) · Brain and Behavior · doi:10.1002/brb3.225 · Cited by 28
“The cortical neuromodulator acetylcholine (ACh) has been implicated in diverse brain processes, both normal and pathological (Bakin and Weinberger 1996; Everitt and Robbins 1997; Nobili and Sannita 1997; Hyde and Crook 2001; Maskos et al. 2005; Sarter et al. 2005).”
Cholinesterase inhibitor, donepezil, improves visual contrast detectability in freely behaving rats
Soma, S., Suematsu, N., & Shimegi, S. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.08.022 · Cited by 28
“Cholinergic neurons in the nucleus basalis of Meynert project o and affect extensive brain areas via acetylcholine (ACh), which lays an important role in various brain functions such as sensation, ttention, learning and memory, and cognition [1–6].”
Wu, M., Liu, C. Z., Barrall, E. A., Rissman, R. A., & Joiner, W. J. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0494-21.2021 · Cited by 27
Cressant, A., Besson, M., Suárez, S., Cormier, A., & Granon, S. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.11.010 · Cited by 28
Kenny, P. J., Hoyer, D., & Koob, G. F. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.02.009 · Cited by 28
“This interpretation is consistent with recent findings showing that the medial habenula and its projections to the interpeduncular nucleus regulate the reward-inhibiting actions of nicotine, as reflected by the involvement of this brain circuit in the ICSS threshold-elevating actions of nicotine (60), whereas the VTA…”
Wilkerson, J. L., Deba, F., Crowley, M. L., Hamouda, A. K., & McMahon, L. R. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108008 · Cited by 29
“Both acute nicotine exposure and nicotine withdrawal in dependent subjects are welldocumented to impact cognitive function (Loughead et al., 2010; Potter and Newhouse, 2008; Maskos et al., 2005).”
BackgroundFoll, B. L., Chefer, S. I., Kimes, A. S., Shumway, D. A., Stein, E. A., Mukhin, A. G., & Goldberg, S. R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.09.036 · Cited by 28
“The α4β2* subtype of nicotinic acetylcholine receptors (nAChRs), located in the midbrain area, has been implicated in mediating the reinforcing effects of nicotine (1).”
BackgroundBiała, G., Kruk-Słomka, M., & Jóźwiak, K. (2013) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-013-0866-z · Cited by 27
“Nicotine action is due to the activation of different types of the nAChRs in the midbrain dopaminergic reward pathway, especially in the ventral tegmental area (VTA) (Maskos et al. 2005; Stolerman and Shoaib 1991).”
Marti, F., Arib, O., Morel, C., Dufresne, V., Maskos, U., Corringer, P., de Beaurepaire, R., & Fauré, P. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.112 · Cited by 36
Paterson, N. E. (2009) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32832c7083 · Cited by 27
“Bupropion is indicated as having antagonist properties at the a3b4 and a4b2 nAChR subtypes (Miller et al., 2002), although it exerts a far higher degree of inhibition at the a3b4 subtype (Alkondon and Albuquerque, 2005).”
BackgroundBourgeois, J., Meas‐Yedid, V., Sourd, A. L., Fauré, P., Pons, S., Maskos, U., Changeux, J., Olivo‐Marín, J., & Granon, S. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr159 · Cited by 34
“…activated in a correlational manner in b2–/– mice exposed to novelty, as these mice have been shown to exhibit altered motivational states (Picciotto et al. 1998; Maskos et al. 2005; Besson et al. 2007; Avale et al. 2011) and increased response to novelty compared with WT mice (Granon et al. 2003).”
BackgroundMethodInfluentialOrthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation
Mohamed, T. S., Jayakar, S. S., & Hamouda, A. K. (2015) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2015.00071 · Cited by 27
“Targeted re-expression of the β2 subunit in the VTA of mice lacking β2 nAChR subunit (β2 KO) was sufficient to reestablish sensitivity to nicotine (Maskos et al., 2005).”
BackgroundTolu, S., Marti, F., Morel, C., Perrier, C., Torquet, N., Pons, S., de Beaurepaire, R., & Fauré, P. (2017) · Scientific Reports · doi:10.1038/srep45116 · Cited by 34
“Nicotine dose was chosen according to previous studies showing that nicotine can be intravenously self-administered at this dose in mice and on the base of our previous works 17,19,24,54 .”
Melis, M., & Pistis, M. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.03.009 · Cited by 27
Cooper, S. Y., & Henderson, B. J. (2020) · Molecules · doi:10.3390/molecules25184223 · Cited by 29
Gardier, A. M. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00098 · Cited by 26
“This strategy was recently applied to study the role of beta2-subunit of the nicotinic acetylcholine receptor (nAChR; Maskos et al., 2005) in mediating the reinforcement properties of nicotine.”
BackgroundMethodDemonstration of functional α4-containing nicotinic receptors in the medial habenula
Fonck, C., Nashmi, R., Salas, R., Zhou, C., Huang, Q., Biasi, M. D., Lester, R. A. J., & Lester, H. A. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.08.021 · Cited by 26
“…the MHb (Wada et al, 1989; Pauly et al., 1996). α4* nAChRs are thought to be necessary and sufficient for the expression of behaviors underlying nicotine addiction including reward, tolerance and sensitization (Tapper et al., 2004, Maskos et al., 2005), but not withdrawal (Salas et al, 2004).”
Farchi, N., Shoham, S., Hochner, B., & Soreq, H. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05249.x · Cited by 26
“, 2002), and nicotine enhances cognitive performance (Maskos et al., 2005).”
BackgroundReynolds, L. M., Faure, P., & Barik, J. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03110-0 · Cited by 26
“ACh provides a complex regulation of reward and motivation behaviors through its actions on dopamine (DA) circuitry [68 – 72].”
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
