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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.
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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
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“Using a lentiviral expression construct as before for most other nAChR subunits, like β2 (Maskos et al., 2005), α4 (Pons et al., 2008) and α6 (Exley et al., 2011), the α5SNP and WT subunits were expressed exclusively in the VTA of mice on an α5 KO background.”
MethodStress‐induced Alternative Splicing Modulations in Brain and Periphery
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“Acknowledgments This work was supported by the European Community’s Grants LSHG-CT2006-037277, LSHM-CT-2006-037378, The German Israel Project (DIP-G 3.2), and the Israel Ministry of Science (3-2589).”
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“1992, 1994); (iii) genetic evidence from knockout and knockin mice implicates a4 and b2 subunits either on dopamine neurons (Picciotto et al. 1998; Maskos et al. 2005) or on GABA neurons (Tapper et al.”
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An innate contribution of human nicotinic receptor polymorphisms to COPD-like lesions
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“Indeed, there is some indication that the interruption of serotonergic transmission through 5-HT2A receptors can block the locomotor response to d-amphetamine and morphine (Sorensen et al., 1993; Moser et al., 1996; McMahon & Cunningham, 2001; Auclair et al., 2004).”
BackgroundMolecular Mechanisms Underlying the Motivational Effects of Nicotine
Brunzell, D. H., & Picciotto, M. R. (2008) · Nebraska Symposium on Motivation/The Nebraska symposium on motivation · doi:10.1007/978-0-387-78748-0_3 · Cited by 22
“Both nicotine-mediated DA release and local selfadministration of nicotine into the VTA can be rescued by lentiviral-mediated expression of the β2 subunit in the VTA of β2KO mice (Maskos et al., 2005).”
BackgroundControlled and localized genetic manipulation in the brain
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“Given these contrasting data, we further explored the role of b4*nAChRs in anxiety-related behaviors, sensitivity to palatable food rewards, and nicotine’s reinforcing properties using intracranial self-administration (ICSA) in the VTA (Maskos et al., 2005; Besson et al., 2006; David et al., 2006; Exley et al., 2011;…”
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Postsynaptic scaffolds for nicotinic receptors on neurons
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“2005), was synthesized after studies suggested the crucial involvement of β2 nAChRs in nicotine dependence (Maskos et al. 2005; Picciotto 1998).”
BackgroundCoutens, B., Moulédous, L., Manta, S., Rampon, C., Lapeyre‐Mestre, M., Roussin, A., Guiard, B. P., & Jouanjus, É. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05198-z · Cited by 20
Chronic Nicotine Exposure has Dissociable Behavioural Effects on Control and Beta2−/− Mice
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The Hair Cell α9α10 Nicotinic Acetylcholine Receptor: Odd Cousin in an Old Family
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“Thus, the differential modulatory control of dopaminergic neuron firing patterns exerted by cholinergic input (Maskos et al., 2005;Mameli-Engvall et al., 2006), might relate to the expression of functionally different neuronal nAChRs.”
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Bellone, C., Loureiro, M., & Lüscher, C. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a039701 · Cited by 18
“Nicotine can directly depolarize DA neurons (Maskos et al. 2005), whereas opioids, benzodiazepines (Tan et al. 2010), cannabinoids (Melis et al. 2004), and γ-hydroxybutyrate (GHB) (Cruz et al. 2004) preferentially inhibit γ-aminobutyric acid (GABA) interneurons, thus causing a disinhibition.”
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“In our future studies, we plan to examine the effects of nicotine on cognitive performance in the NP rat line.”
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Varenicline use in patients with mental illness: an update of the evidence
Purvis, T. L., Nelson, L. A., & Mambourg, S. (2010) · Expert Opinion on Drug Safety · doi:10.1517/14740331003657133 · Cited by 19
“Nicotine acts as a full agonist and stimulates the release of dopamine through direct activation of the nicotinic acetylcholine receptors (nAChRs), specifically a4b2 receptor subtype, in the VTA (Figure 1) [22,23-25].”
BackgroundPonzoni, L., Moretti, M., Braida, D., Zoli, M., Clementi, F., Viani, P., Sala, M., & Gotti, C. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.02.001 · Cited by 20
Novel Pharmacological Approaches to Drug Abuse Treatment
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“The a4b2* nAChR is the most abundant nAChR type found in mammalian brains and is thought to be the primary mediator of nicotine dependence (Maskos et al. 2005; Picciotto et al. 1998).”
BackgroundVarenicline in smoking cessation
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Suárez, S., Amadon, A., Giacomini, E., Wiklund, A.-K., Changeux, J., Bihan, D. L., & Granon, S. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1338-x · Cited by 19
“A bolus of nicotine given in the general circulation produces both localized dopaminergic activation (e.g., Champtiaux et al. 2003; Marubio et al. 2003; Maskos et al. 2005; Mameli-Engvall et al. 2006) and distributed effects such as the release of other neurotransmitters, the synthesis of transcription factors (Hirema…”
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“We showed that re-expression of the 2 subunit in the mesolimbic pathway of adult 2 / mice restored wild-type phenotypes related to this pathway (47).”
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Jiang, J. W., Li, X., Hu, A., Zhou, G., Gao, Y.-H., Xu, C., Wu, X., & Wang, H. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1670883 · Cited by 24
Nicotinic Receptors Underlying Nicotine Dependence: Evidence from Transgenic Mouse Models
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“Midbrain DA neurons require acetylcholine (ACh) for the switch from tonic to phasic firing, which is essential for normal instrumental learning (Maskos et al. 2005; Maskos 2008; Zweifel et al. 2009).”
Nicotine Addiction: Mechanisms and Consequences
Rosenthal, D. G., Weitzman, M. L., & Benowitz, N. L. (2011) · International Journal of Mental Health · doi:10.2753/imh0020-7411400102 · Cited by 18
“tal area (VTA) of the brain reinstates nicotine-mediated behavior [14, 15].”
BackgroundOff the Beaten Path: Drug Addiction and the Pontine Laterodorsal Tegmentum
Kohlmeier, K. A. (2013) · ISRN Neuroscience · doi:10.1155/2013/604847 · Cited by 20
“The β2 nicotinic receptor located putatively on DA VTA cells was shown to be critical to excitability of DA VTA neurons as the nicotine-induced switch from tonic firing to burst firing was prevented in mice lacking the β2 receptor but rescued in animals in which the β2 receptor was restored selectively to the VTA via…”
Siciliano, C. A., McIntosh, J. M., Jones, S. R., & Ferris, M. J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.06.028 · Cited by 21
“However, studies have shown that nAChRs in the NAc core possess little to no role in maintaining nicotine reinforcement in animals well-trained for nicotine self-administration (Corrigall et al., 1994; Maskos et al., 2005).”
BackgroundLaikowski, M. M., Reisdorfer, F., & Moura, S. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180410105135 · Cited by 17
MacLean, R. R., Waters, A. J., Brede, E., & Sofuoglu, M. (2018) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2665 · Cited by 17
“Preclinical studies have established the role of α4β2 nAChRs in nicotine reinforcement (Maskos et al., 2005; Tapper et al., 2004), and drugs that target α4β2 nAChRs, such as varenicline, are associated with decreased nicotine intake in rodents (George, Lloyd, Carroll, Damaj, & Koob, 2011) and increased smoking cessati…”
BackgroundWiklund, A., Granon, S., Cloëz-Tayarani, I., Fauré, P., Sourd, A. L., Sundman, E., Changeux, J., & Eriksson, L. I. (2008) · Anesthesiology · doi:10.1097/aln.0b013e31818a379a · Cited by 17
“However, 2 subunit gene re-expression experiments have shown that the neuronal, physiologic, and behavioral phenotypes are not caused by the actual absence of 2-containing nAChRs, but rather by their deficit in defined circuits involving, in particular, dopaminergic neurons in the ventral tegmental area.(24)”
BackgroundMethodInfluentialDesign, Synthesis and Discovery of Picomolar Selective α4β2 Nicotinic Acetylcholine Receptor Ligands
Yenugonda, V. M., Xiao, Y., Levin, E. D., Rezvani, A. H., Tran, T. P., Al‐Muhtasib, N., Sahibzada, N., Xie, T., Wells, C., Slade, S. K., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4008455 · Cited by 17
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“DOI: 10.7554/eLife.25651 1 of 23 tegmental area (VTA) of b2-knockout mice rescues nicotine-seeking behavior and nicotine-induced dopamine release (Maskos et al., 2005).”
BackgroundInfluentialZaveri, N. T., Bertrand, S., Yasuda, D. M., & Bertrand, D. (2014) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntu170 · Cited by 16
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“, 1998) or into the ventral tegmental area (Maskos et al., 2005).”
BackgroundBrain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler
Esterlis, I., Mitsis, E. M., Batis, J. C., Bois, F., Picciotto, M. R., Stiklus, S. M., Kloczynski, T., Perry, E. B., Seibyl, J. P., McKee, S. A., et al. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710001227 · Cited by 17
“Nicotine binds to beta-2 subunit-containing nicotinic acetylcholine receptors (β2*-nAChRs; where * represents other subunits that may also be part of the receptor), and preclinical studies suggest that these receptors are critical for initiating the events leading to tobacco smoking addiction (Epping-Jordan et al. 199…”
BackgroundAdvances in smoking cessation pharmacotherapy: Non-nicotinic approaches in animal models
Smith, L. C., & George, O. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108225 · Cited by 18
Nicotinic receptor agonist-induced salivation and its cellular mechanism in parotid acini of rats
Iida, T., Ono, K., Inagaki, T., Hosokawa, R., & Inenaga, K. (2011) · Autonomic Neuroscience · doi:10.1016/j.autneu.2011.01.003 · Cited by 16
“Since nicotine addiction is reported to be mediated through β2-containing nicotinic receptor in the brain in experimentally nicotine-administrated animals (Maskos et al., 2005), cytisine may not show any addiction response.”
BackgroundSimmons, S. J., & Gould, T. J. (2014) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12171 · Cited by 18
“Targeted lentiviral expression of the b2 subunit in the VTA of b2 / mice restored nicotine self-administration(31,33,34) and increased phasic DA release in the NAcc after nicotine administration.(31) Additionally, mice acquire conditioned place preference (CPP) to nicotine,(60) as evidenced by animals spending signifi…”
BackgroundEarly Signs of Pathological Cognitive Aging in Mice Lacking High-Affinity Nicotinic Receptors
Konsolaki, E., Tsakanikas, P., Polissidis, A., Stamatakis, A., & Skaliora, I. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00091 · Cited by 15
“Two-way ANOVA was performed Frontiers in Aging Neuroscience | www.frontiersin.org 3 April 2016 | Volume 8 | Article 91 to evaluate the effect of age and genotype on marble burying performance.”
BackgroundMethodInfluentialStructural basis for allosteric agonism of human α7 nicotinic acetylcholine receptors
Liu, S., Zheng, Y., Chen, H., Li, X., Yan, Q., Mu, W., Fu, Y., Chen, H., Hou, H., Liu, L., et al. (2025) · Cell Discovery · doi:10.1038/s41421-025-00788-y · Cited by 15
DRD2 -related TaqIA polymorphism modulates motivation to smoke
Zuo, Y., Gilbert, D. G., Rabinovich, N. E., Riise, H., Needham, R., & Huggenvik, J. I. (2009) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntp141 · Cited by 16
“…1989 ), psychomotor ( Clarke, Fu, Jakubovic, & Fibiger, 1988 ; Wise & Bozarth, 1987 ), cognitive ( Koob & Le Moal, 2001 ; Levin & Simon, 1998 ; Maskos et al., 2005 ), and affective effects of nicotine ( Cinciripini et al., 2004 ; David et al., 2003 ; Gilbert, 1995 ; Gilbert et al., 2004 ;…”
Zhu, M., Rogers, N. G., Jahad, J. V., & Herman, M. A. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.2087-22.2023 · Cited by 16
Sagara, H., Kitamura, Y., Yae, T., Shibata, K., Suemaru, K., Sendo, T., Araki, H., & Gomita, Y. (2008) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08168fp · Cited by 15
Minguez, T., Nielsen, B. E., Shoemark, D. K., Gotti, C., Sessions, R. B., Mulholland, A. J., Bouzat, C., Wonnacott, S., Gallagher, T. C., Bermúdez, I., et al. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15389 · Cited by 13
Virus-Delivered RNA Interference in Mouse Brain to Study Addiction-Related Behaviors
Lasek, A. W., & Azouaou, N. (2009) · Methods in molecular biology · doi:10.1007/978-1-60761-058-8_17 · Cited by 15
Fait, B. W., Thompson, D. C., Mose, T. N., Jatlow, P. I., Jordt, S. E., Picciotto, M. R., & Mineur, Y. S. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.07.027 · Cited by 14
“This behavioral model is also of interest because it requires the expression of nicotinic acetylcholine receptors (nAChRs) containing the β2 subunit in mesostriatal neurons, which are essential for behaviors related to nicotine addiction [21,23] and are upregulated by menthol after long term exposure [15].”
Tritschler, L., Kheirbek, M. A., Dantec, Y. L., Mendez‐David, I., Guilloux, J., Faye, C., Doan, J., Pham, T. H., Hen, R., David, D. J. P., et al. (2017) · Neuroscience Research · doi:10.1016/j.neures.2017.12.002 · Cited by 14
Overview of Nicotine Withdrawal and Negative Reinforcement (Preclinical)
George, O., & Koob, G. F. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802574-1.00001-6 · Cited by 15
Comparative effects of dextromethorphan and dextrorphan on nicotine discrimination in rats
Wright, M. J., Vann, R. E., Gamage, T. F., Damaj, M. I., & Wiley, J. L. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.09.020 · Cited by 16
“…and subsequent the reinforcing effects of nicotine, are dependent upon both the α4 and β2 subunits (Picciotto et al., 1998; Tapper et al., 2004; Maskos et al., 2005), although Glick et al. (2001) also hypothesized involvement of α3β4* nicotinic receptor action in the reinforcing actions of…”
BackgroundVarenicline: progress in smoking cessation treatment
Glover, E. D., & Rath, J. M. (2007) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.8.11.1757 · Cited by 14
“The nicotinic acetylcholine receptor (nAChR) system in the ventral tegmental area (VTA) performs a crucial role in nicotine reinforcement [33] , mediated in particular by α 4 β 2 receptors [14,33-39] .”
BackgroundAhmed, S. H., Bobashev, G., & Gutkin, B. S. (2007) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2007.01.008 · Cited by 14
Liu, Y., Richardson, J. R., Tran, T. P., Al‐Muhtasib, N., Xie, T., Yenugonda, V. M., Sexton, H. G., Rezvani, A. H., Levin, E. D., Sahibzada, N., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4000374 · Cited by 13
Grieder, T. E., George, O., Yee, M., Bergamini, M., Chwalek, M., Maal‐Bared, G., Vargas-Pérez, H., & van der Kooy, D. (2017) · European Journal of Neuroscience · doi:10.1111/ejn.13605 · Cited by 15
“…a2-a10 and b2–b4, that combine to form a large variety of homomeric and heteromeric receptors (Le Novere et al., 2002), of which those containing the a4 and b2 subunits have been implicated most often in nicotine motivation (Picciotto et al., 1998; Tapper et al., 2004; Maskos et al., 2005).”
BackgroundHay, Y. A., Naudé, J., Fauré, P., & Lambolez, B. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy148 · Cited by 11
Zhang, H. J., Zammit, M. D., Kao, C.-M., Govind, A. P., Mitchell, S. J., Holderman, N., Bhuiyan, M. P. I., Freifelder, R. H., Kucharski, A., Zhuang, X., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.2484-21.2022 · Cited by 12
Li, Q., Nemecz, Á., Aymé, G., de la Bâtie, G. D., Prevost, M. S., Pons, S., Barilone, N., Baachaoui, R., Maskos, U., Lafaye, P. J., et al. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04779-8 · Cited by 13
Miller, M. B., Wilson, R. S., Lam, T. T., Nairn, A. C., & Picciotto, M. R. (2018) · Proteomes · doi:10.3390/proteomes6040042 · Cited by 13
Nagai, T., Nabeshima, T., & Yamada, K. (2008) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08r04fm · Cited by 14
Kedmi, M., & Orr-Urtreger, A. (2007) · Physiological Genomics · doi:10.1152/physiolgenomics.00155.2006 · Cited by 14
“These receptors mediate the effects of the endogenous neurotransmitter, acetylcholine, and the tobacco alkaloid, nicotine, and are involved in a wide range of neuronal processes, including cognition, memory (28, 30, 34), and autonomic nervous system functions (53, 55).”
BackgroundThe interpeduncular nucleus blunts the rewarding effect of nicotine
Jehl, J., Ciscato, M., Vicq, É., Guyon, N., de la Bâtie, G. D., Mondoloni, S., Frangieh, J., Mohayyaei, M., Nguyen, C., Pons, S., et al. (2023) · Neuron · doi:10.1016/j.neuron.2025.03.035 · Cited by 12
Mantione, M. E., Micheloni, S., Alcaino, C., New, K., Mazzaferro, S., & Bermúdez, I. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.172 · Cited by 12
β2 nAChR Activation on VTA DA Neurons Is Sufficient for Nicotine Reinforcement in Rats
Walker, N. B., Yan, Y., Tapia, M. A., Tucker, B. R., Thomas, L. N., George, B. E., West, A. M., Marotta, C. B., Lester, H. A., Dougherty, D. A., et al. (2023) · eNeuro · doi:10.1523/eneuro.0449-22.2023 · Cited by 15
“Changeux and colleagues reported that re-expression of b 2 subunits in the VTA of b 2 KO mice was sufficient to restore intracranial (intra-VTA) self-administration of nicotine (Maskos et al., 2005).”
BackgroundLee, A. M., Arreola, A. C., Kimmey, B. A., & Schmidt, H. D. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.08.016 · Cited by 13
“Consistent with these findings, mutant mice lacking β2* nAChRs self-administer less nicotine than wildtype controls, deficits that are reversed following viral-mediated re-expression of β2 nAChR subunits in the ventral tegmental area [50-52].”
BackgroundMadsen, H. B., Koghar, H. S., Pooters, T., Massalas, J. S., Drago, J., & Lawrence, A. J. (2014) · Addiction Biology · doi:10.1111/adb.12148 · Cited by 15
“…et al. 1998; Grady et al. 2001, 2002) and behaviours related to nicotine reward and reinforcement (Picciotto et al. 1998; Epping-Jordan et al. 1999; Maskos et al. 2005; Walters et al. 2006; Pons et al. 2008; Mineur et al. 2009). α4 subunits are reportedly the principal partner of β2 subunits, and…”
BackgroundFarquhar, M. J., Latimer, M. P., & Winn, P. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2452-8 · Cited by 12
Dorsomedial prefrontal cortex neurons encode nicotine-cue associations
Struik, R. F., Marchant, N. J., de Haan, R., Terra, H., van Mourik, Y., Schetters, D., Carr, M. R., van der Roest, M., Heistek, T. S., & Vries, T. J. D. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0449-x · Cited by 14
Jonkman, S., & Markou, A. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.02.030 · Cited by 13
Renda, A., & Nashmi, R. (2012) · Journal of Visualized Experiments · doi:10.3791/3516 · Cited by 12
Molles, B. E., Maskos, U., Pons, S., Besson, M., Guiard, P., Guilloux, J., Evrard, A., Cormier, A., Mameli-Engvall, M., Cloëz-Tayarani, I., et al. (2006) · Journal of Molecular Neuroscience · doi:10.1385/jmn:30:1:105 · Cited by 12
“Our lentiviral expression vector contains a bicistronic cassette (Maskos et al., 2005) simultaneously expressing the mouse 2 subunit and the enhanced green fluorescent protein (eGFP) using an intervening internal ribosome entry site sequence (Clontech).”
BackgroundMethodInfluentialAnand, R., Stephanie, A., Ponath, G. D., Jordan, I., Nasir, M. I., & Susan, B. (2011) · InTech eBooks · doi:10.5772/20752 · Cited by 11
Cholinergic modulation of dopamine release drives effortful behaviour
Touponse, G. C., Pomrenze, M. B., Yassine, T. A., Denomme, N., WANG, M. C., Mehta, V., Zhang, Z., Malenka, R. C., & Eshel, N. (2026) · Nature · doi:10.1038/s41586-025-10046-6 · Cited by 33
Bozinoff, N., & Foll, B. L. (2018) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2018.1507736 · Cited by 11
“The focus has been initially on the role of β2 and α4 subunits, notably based on the findings that β2 subunit deletion decreases sensitivity to nicotine’s reinforcing effects [11] and the fact that α4 subunit overexpression increases sensitivity to nicotine reinforcement [51].”
BackgroundRole of CYP2B6 pharmacogenomics in bupropion-mediated smoking cessation
Tran, A. X. V., COOPERDEHOFF, R., & Gupta, S. V. (2018) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12783 · Cited by 12
Neurochemistry of Parkinson's disease
Rao, J. (2007) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)83007-7 · Cited by 11
Kishi, T., Ikeda, M., Kitajima, T., Yamanouchi, Y., Kinoshita, Y., Kawashima, K., Okochi, T., Inada, T., Ozaki, N., & Iwata, N. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-008-0114-8 · Cited by 11
“Firstly, beta2 subunits in the ventral tegmental area in mutant mice showed alternation of dopamine release in the nucleus accumbens and changes in cognitive functions such as navigation and exploratory behaviour compared with wild mice (Maskos et al. 2005).”
BackgroundGautier, A., Ouaraki, H. E., Bazin, N., Salam, S., Vodjdani, G., Bourgoin, S., Pezet, S., Bernard, J., & Hamon, M. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.10.016 · Cited by 11
“microinjecting recombinant lentiviral particles in central nervous tissues (Bensadoun et al., 2000; Maskos et al., 2005; Meunier et al., 2007) to express transfected genes within anatomically defined areas, indicating a much more restricted diffusion of lentiviral particles compared to microinjected chemicals (see Jol…”
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
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