Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine
Abstract
Release of the neurotransmitter dopamine in the mesolimbic system of the brain mediates the reinforcing properties of several drugs of abuse, including nicotine. Here we investigate the contribution of the high-affinity neuronal nicotinic acetylcholine receptor to the effects of nicotine on the mesolimbic dopamine system in mice lacking the beta2 subunit of this receptor. We found that nicotine stimulates dopamine release in the ventral striatum of wild-type mice but not in the ventral striatum of beta2-mutant mice. Using patch-clamp recording, we show that mesencephalic dopaminergic neurons from mice without the beta2 subunit no longer respond to nicotine, and that self-administration of nicotine is attenuated in these mutant mice. Our results strongly support the idea that the beta2-containing neuronal nicotinic acetylcholine receptor is involved in mediating the reinforcing properties of nicotine.
Integrity signals
Registry
Cites
Statistics
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?
β2*-nAChRs are a critical neural substrate mediating the effects of nicotine in brain.
“In recent years evidence has emerged that the β2*-nAChRs are a critical neural substrate mediating the effects of nicotine in brain.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [22]
The β2-subunit has been linked primarily to the reinforcing effects of nicotine and combines with the α3-6 subunits.
“Notably, the β2-subunit has been linked primarily to the reinforcing effects of nicotine22, 83, 84 and combines with the α3-6 subunits.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [22]
nAChRs containing the β2 subunit are essential for nicotine to depolarize DA cell bodies in the VTA and increase their firing rate.
“Electrophysiological studies have shown that nAChRs containing the β2 subunit are essential for the ability of nicotine to depolarize DA cell bodies in the VTA and to increase their firing rate (Picciotto et al. 1998;Zhou et al. 2001).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Picciotto et al. 1998
Knockout of the β2 subunit abolishes nicotine-mediated DA release, nicotine-induced locomotor activation, nicotine self-administration, and nicotine place preference.
“Knockout of the β2 subunit abolishes nicotine-mediated DA release (Picciotto et al. 1998;Grady et al. 2001), nicotine-induced locomotor activation (King et al. 2004), nicotine selfadministration (Picciotto et al. 1998;Maskos et al. 2005), and nicotine place preference (Walters et al. 2006;Brunzell et al. 2009;Mineur et al. 2009a).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Picciotto et al. 1998
nAChRs containing β2-subunits (β2*-nAChRs) mediate the reinforcing properties of nicotine.
“In particular, nAChRs containing  2 -subunits ( 2 *-nAChRs) the most prevalent subtype, mediate the reinforcing properties of nicotine.”
From Human Tobacco Smokers in Early Abstinence Have Higher Levels of β<sub>2</sub>* Nicotinic Acetylcholine Receptors than Nonsmokers (2006) · cites this paper as Picciotto et al., 1998
Acute activation of nAChRs by nicotine can stimulate the firing of DA neurons.
“As noted in Section 1, it is clear that acute activation of nAChRs by nicotine can stimulate the firing of DA neurons (Grenhoff et al., 1986; Klink et al., 2001; Picciotto et al., 1998; Svensson et al., 1990).”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Picciotto et al., 1998
β2 subunit knockout mice do not self-administer nicotine.
“2 subunit knockout mice do not self-administer nicotine (Picciotto et al., 1998).”
From Chronic Sazetidine-A at Behaviorally Active Doses Does Not Increase Nicotinic Cholinergic Receptors in Rodent Brain (2012) · cites this paper as Picciotto et al., 1998
Mice lacking α4, α6, and/or β2 nAChR subunits do not self-administer nicotine, and restoring these subunits in the ventral tegmental area of knockout mice restores nicotine self-administration.
“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 Picciotto et al., 1998
β2, α4, or α6 nAChR knockout mice fail to self-administer nicotine.
“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 Picciotto et al., 1998
Genetically modified mice lacking the β2 subtype of nAChRs showed normal levels of anxiety in the elevated plus maze.
“genetically modified mice that lack β2 subtype of nAChRs showed normal levels of anxiety in the EPM (Picciotto et al., 1998)”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Picciotto et al., 1998
Cites
Drugs of abuse: anatomy, pharmacology and function of reward pathways
Koob, G. F. (1992) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(92)90060-j · Cited by 2,070 · see citing works
Effects 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 · see citing works
Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors
McGehee, D. S., Heath, M. J. S., Gelber, S., Devay, P., & Role, L. W. (1995) · Science · doi:10.1126/science.7569895 · Cited by 1,070 · see citing works
The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine
Corrigall, W. A., Franklin, K. B. J., Coen, K. M., & Clarke, P. B. S. (1992) · Psychopharmacology · doi:10.1007/bf02245149 · Cited by 829 · see citing works
Nicotinic Receptors in the Development and Modulation of CNS Synapses
Role, L. W., & Berg, D. K. (1996) · Neuron · doi:10.1016/s0896-6273(00)80134-8 · Cited by 762 · see citing works
Grace, A., & Onn, S. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-10-03463.1989 · Cited by 720 · see citing works
Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain
Picciotto, M. R., Zoli, M., Léna, C., Bessis, A., Lallemand, Y., LeNovère, N., Vincent, P., Pich, E. M., Brûlet, P., & Changeux, J.-P. (1995) · Nature · doi:10.1038/374065a0 · Cited by 668 · see citing works
Self-citationMolecular and cellular aspects of nicotine abuse
Dani, J. A., & Heinemann, S. (1996) · Neuron · doi:10.1016/s0896-6273(00)80112-9 · Cited by 605 · see citing works
Luetje, C., & Patrick, J. (1991) · The Journal of Neuroscience · doi:10.1523/jneurosci.11-03-00837.1991 · Cited by 558 · see citing works
Nisell, M., Nomikos, G. G., & Svensson, T. H. (1994) · Synapse · doi:10.1002/syn.890160105 · Cited by 510 · see citing works
Mansour, A., Meador‐Woodruff, J. H., Bunzow, J., Civelli, O., Akil, H., & Watson, S. J. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-08-02587.1990 · Cited by 467 · see citing works
Le Novere, N., Zoli, M., & Changeux, J. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01206.x · Cited by 385 · see citing works
Self-citationGrady, S., Marks, M. J., Wonnacott, S., & Collins, A. C. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb08322.x · Cited by 350 · see citing works
Common Neural Substrates for the Addictive Properties of Nicotine and Cocaine
Pich, E. M., Pagliusi, S. R., Tessari, M., Talabot‐Ayer, D., van Huijsduijnen, R. H., & Chiamulera, C. (1997) · Science · doi:10.1126/science.275.5296.83 · Cited by 347 · see citing works
Self-citationD-1 dopamine receptors in the rat brain: a quantitative autoradiographic analysis
Dawson, T., Gehlert, D. R., McCabe, R. T., Barnett, A., & Wamsley, J. K. (1986) · Journal of Neuroscience · doi:10.1523/jneurosci.06-08-02352.1986 · Cited by 341 · see citing works
Clarke, P. B., Fu, D. S., Jakubovic, A., & Fibiger, H. C. (1988) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22152-8 · Cited by 318 · see citing works
Calabresi, P., Lacey, M. G., & North, R. A. (1989) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1989.tb16873.x · Cited by 285 · see citing works
Blaha, C. D., Allen, L., Das, S., Inglis, W. L., LATIMER, M. L., Vincent, S., & Winn, P. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-02-00714.1996 · Cited by 216 · see citing works
Reinhard, J. F., Smith, G. K., & Nichol, C. A. (1986) · Life Sciences · doi:10.1016/0024-3205(86)90395-4 · Cited by 201 · see citing works
Cigarette smokers self-administer intravenous nicotine
Henningfield, J. E., Miyasato, K., & Jasinski, D. R. (1983) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(83)90099-0 · Cited by 158 · see citing works
Nicotine-induced conditioned place preference and conditioned place aversion in mice
Risinger, F. O., & Oakes, R. A. (1995) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)00007-j · Cited by 142 · see citing works
Behavioural and pharmacokinetic studies on nicotine, cytisine and lobeline
Reavill, C. A., Walther, B., Stolerman, I. P., et al. (1990) · Neuropharmacology · doi:10.1016/0028-3908(90)90022-j · Cited by 141 · see citing works
Nicotine psychopharmacology: Addiction, cognition and neuroadaptation
Stolerman, I. P., Mirza, N. R., & Shoaib, M. (1995) · Medicinal Research Reviews · doi:10.1002/med.2610150105 · Cited by 102 · see citing works
Izenwasser, S., Jacocks, H. M., Rosenberger, J. G., & Cox, B. M. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb08192.x · Cited by 72 · see citing works
Memo, M., Castelletti, L., Missale, C., et al. (1986) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1986.tb13075.x · Cited by 68 · see citing works
Distribution of cocaine recognition sites in monkey brain: I. In vitro autoradiography with [3H]CFT
Kaufman, M. J., Spealman, R. D., & Madras, B. K. (1991) · Synapse · doi:10.1002/syn.890090304 · Cited by 60 · see citing works
Intravenous cocaine self-administration in the C57BL/6J mouse
Grahame, N. J., Phillips, T. J., Burkhart‐Kasch, S., & Cunningham, C. L. (1995) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)00047-z · Cited by 43 · see citing works
Nicotine reinforcement in rats with histories of cocaine self-administration
Tessari, M., Valerio, E., Chiamulera, C., et al. (1995) · Psychopharmacology · doi:10.1007/bf02245640 · Cited by 40 · see citing works
Rimondini, R., O'Connor, W. T., Ferré, S., et al. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90043-4 · Cited by 7 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
Picciotto, M. R., Higley, M. J., & Mineur, Y. S. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.036 · Cited by 1,404 · see citing works
Self-citationA 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 · see citing works
Self-citationThe genetics of addictions: uncovering the genes
Goldman, D., Oroszi, G., & Ducci, F. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1635 · Cited by 1,099 · see citing works
Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics
Benowitz, N. L. (2009) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094742 · Cited by 979 · see citing works
Varenicline: An α4β2 Nicotinic Receptor Partial Agonist for Smoking Cessation
Coe, J. W., Brooks, P. R., Vetelino, M. G., Wirtz, M. C., Arnold, E. P., Huang, J., Sands, S. B., Davis, T. I., Lebel, L. A., Fox, C. B., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050069n · Cited by 930 · see citing works
Guidelines on nicotine dose selection for in vivo research
Matta, S. G., Balfour, D. J., Benowitz, N. L., Boyd, R. T., Buccafusco, J. J., Caggiula, A. R., Craig, C. R., Collins, A. C., Damaj, M. I., Donny, E. C., et al. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0441-0 · Cited by 824 · see citing works
Self-citationLong-term potentiation of excitatory inputs to brain reward areas by nicotine
Mansvelder, H. D., & McGehee, D. S. (2000) · Neuron · doi:10.1016/s0896-6273(00)00042-8 · Cited by 720 · see citing works
Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas
Mansvelder, H. D., Keath, J. R., & McGehee, D. S. (2002) · Neuron · doi:10.1016/s0896-6273(02)00625-6 · Cited by 701 · see citing works
Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization
Tapper, A. R., McKinney, S. L., Nashmi, R., Schwarz, J., Deshpande, P., Labarca, C., Whiteaker, P., Marks, M. J., Collins, A. C., & Lester, H. A. (2004) · Science · doi:10.1126/science.1099420 · Cited by 686 · see citing works
Habenular α5 nicotinic receptor subunit signalling controls nicotine intake
Fowler, C. D., Lu, Q., Johnson, P. M., Marks, M. J., & Kenny, P. J. (2011) · Nature · doi:10.1038/nature09797 · Cited by 663 · see citing works
Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors
Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J.-P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., et al. (2005) · Nature · doi:10.1038/nature03694 · Cited by 566 · see citing works
The dynamic effects of nicotine on the developing brain
Dwyer, J. B., McQuown, S. C., & Leslie, F. M. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.02.003 · Cited by 559 · see citing works
Rollema, H., Chambers, L. K., Coe, J. W., Glowa, J., Hurst, R. S., Lebel, L. A., Lu, Y., Mansbach, R. S., Mather, R. J., Rovetti, C. C., et al. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.10.016 · Cited by 533 · see citing works
Effect of nicotine and nicotinic receptors on anxiety and depression
Picciotto, M. R., Brunzell, D. H., & Caldarone, B. J. (2002) · Neuroreport · doi:10.1097/00001756-200207020-00006 · Cited by 483 · see citing works
Self-citationCholinergic Interneurons Control Local Circuit Activity and Cocaine Conditioning
Witten, I. B., Lin, S.-C., Brodsky, M., Prakash, R., Diester, I., Anikeeva, P., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K. (2010) · Science · doi:10.1126/science.1193771 · Cited by 467 · see citing works
Nicotine addiction and nicotinic receptors: lessons from genetically modified mice
Changeux, J.-P. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2849 · Cited by 453 · see citing works
Self-citationPICCIOTTO, M., ADDY, N., MINEUR, Y., & BRUNZELL, D. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.12.005 · Cited by 451 · see citing works
Self-citationNeural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal
S. Watkins, G. F. K. (2000) · Nicotine & Tobacco Research · doi:10.1080/14622200050011277 · Cited by 424 · see citing works
Alternate stoichiometries of α4β2 nicotinic acetylcholine receptors
Nelson, M. E., Kuryatov, A., Choi, C. H., Zhou, Y., & Lindstrom, J. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.2.332 · Cited by 422 · see citing works
Zoli, M., Moretti, M., Zanardi, A., McIntosh, J. M., Clementi, F., & Gotti, C. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08785.2002 · Cited by 407 · see citing works
Self-citationRollema, H., Coe, J. W., Chambers, L. K., Hurst, R. S., Stahl, S. M., & Williams, K. E. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2007.05.003 · Cited by 400 · see citing works
Nides, M. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.15.1561 · Cited by 390 · see citing works
General anaesthetic actions on ligand-gated ion channels
Krasowski, M. D., & Harrison, N. L. (1999) · Cellular and Molecular Life Sciences (CMLS) · doi:10.1007/s000180050371 · Cited by 384 · see citing works
Neurobiology of Nicotine Addiction: Implications for Smoking Cessation Treatment
Benowitz, N. L. (2008) · The American Journal of Medicine · doi:10.1016/j.amjmed.2008.01.015 · Cited by 385 · see citing works
Nicotine addiction and comorbidity with alcohol abuse and mental illness
Dani, J. A., & Harris, R. A. (2005) · Nature Neuroscience · doi:10.1038/nn1580 · Cited by 382 · see citing works
Reward, addiction, withdrawal to nicotine
De Biasi, M., & Dani, J. A. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113734 · Cited by 366 · see citing works
“…mechanistic actions underlie nicotine’s ability to enhance reward from brain stimulation, reinforce conditioned place preference, and support self-administration (Corrigall 1999, Dani et al. 2009, Dani & Harris 2005, Mameli-Engvall et al. 2006, Picciotto et al. 1998, Stolerman & Shoaib 1991).”
BackgroundChronic Exposure to Nicotine Upregulates the Human α4β2 Nicotinic Acetylcholine Receptor Function
Buisson, B., & Bertrand, D. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-06-01819.2001 · Cited by 361 · see citing works
Wooltorton, J. R. A., Pidoplichko, V. I., Broide, R. S., & Dani, J. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03176.2003 · Cited by 363 · see citing works
Nicotinic receptors in the brain. Links between molecular biology and behavior
Picciotto, M. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00146-3 · Cited by 354 · see citing works
Govind, A. P., Vezina, P., & Green, W. N. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.06.011 · Cited by 338 · see citing works
Smoking and structural brain deficits: a volumetric MR investigation
Gallinat, J., Meisenzahl, E., Jacobsen, L. K., Kalus, P., Bierbrauer, J., Kienast, T., Witthaus, H., Leopold, K., Seifert, F., Schubert, F., et al. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05050.x · Cited by 330 · see citing works
Brain nicotinic receptors: structure and regulation, role in learning and reinforcement
Changeux, J.-P., Bertrand, D., Corringer, P.-J., Dehaene, S., Edelstein, S., Léna, C., Le Novère, N., Marubio, L., Picciotto, M., & Zoli, M. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00040-4 · Cited by 322 · see citing works
Self-citationLe Foll, B., Piper, M. E., Fowler, C. D., Tonstad, S., Bierut, L., Lu, L., Jha, P., & Hall, W. D. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00346-w · Cited by 316 · see citing works
Pons, S., Fattore, L., Cossu, G., Tolu, S., Porcu, E., McIntosh, J. M., Changeux, J. P., Maskos, U., & Fratta, W. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3918-08.2008 · Cited by 312 · see citing works
Self-citationSalas, R., Sturm, R., Boulter, J., & De Biasi, M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4934-08.2009 · Cited by 310 · see citing works
Donny, E. C., Chaudhri, N., Caggiula, A. R., Evans-Martin, F. F., Booth, S., Gharib, M. A., Clements, L. A., & Sved, A. F. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1473-3 · Cited by 304 · see citing works
Hierarchical Control of Dopamine Neuron-Firing Patterns by Nicotinic Receptors
Mameli-Engvall, M., Evrard, A., Pons, S., Maskos, U., Svensson, T. H., Changeux, J.-P., & Faure, P. (2006) · Neuron · doi:10.1016/j.neuron.2006.05.007 · Cited by 296 · see citing works
Self-citationChaudhri, N., Caggiula, A. R., Donny, E. C., Palmatier, M. I., Liu, X., & Sved, A. F. (2006) · Psychopharmacology · doi:10.1007/s00213-005-0178-1 · Cited by 271 · see citing works
Nashmi, R., Xiao, C., Deshpande, P., McKinney, S., Grady, S. R., Whiteaker, P., Huang, Q., McClure-Begley, T., Lindstrom, J. M., Labarca, C., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2199-07.2007 · Cited by 274 · see citing works
Weiss, R. B., Baker, T. B., Cannon, D. S., von Niederhausern, A., Dunn, D. M., Matsunami, N., Singh, N. A., Baird, L., Coon, H., McMahon, W. M., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000125 · Cited by 271 · see citing works
Kenny, P. J., & Markou, A. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300905 · Cited by 261 · see citing works
Windows of vulnerability to psychopathology and therapeutic strategy in the adolescent rodent model
Adriani, W., & Laviola, G. (2004) · Behavioural Pharmacology · doi:10.1097/00008877-200409000-00005 · Cited by 267 · see citing works
Nicotine upregulates its own receptors through enhanced intracellular maturation
Sallette, J., Pons, S., Devillers-Thiery, A., Soudant, M., Prado de Carvalho, L., Changeux, J.-P., & Corringer, P. J. (2005) · Neuron · doi:10.1016/j.neuron.2005.03.029 · Cited by 261 · see citing works
Self-citationNicotine as a modulator of behavior: beyond the inverted U
Picciotto, M. R. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00230-x · Cited by 257 · see citing works
Self-citationNicotine addiction: the possible role of functional upregulation
Buisson, B., & Bertrand, D. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01979-9 · Cited by 254 · see citing works
The role of the brain reward system in depression
Naranjo, C. A., Tremblay, L. K., & Busto, U. E. (2001) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(01)00156-7 · Cited by 245 · see citing works
Exley, R., Clements, M. A., Hartung, H., McIntosh, J. M., & Cragg, S. J. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301617 · Cited by 242 · see citing works
Meaningful silences: how dopamine listens to the ACh pause
Cragg, S. J. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.01.003 · Cited by 245 · see citing works
Marubio, L. M., Gardier, A. M., Durier, S., David, D., Klink, R., Arroyo‐Jimenez, M. M., McIntosh, J. M., Rossi, F., Champtiaux, N., Zoli, M., et al. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02564.x · Cited by 242 · see citing works
Self-citationImpaired attention is central to the cognitive deficits observed in alpha 7 deficient mice
Young, J. W., Crawford, N., Kelly, J. S., Kerr, L. E., Marston, H. M., Spratt, C., Finlayson, K., & Sharkey, J. (2007) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2006.03.008 · Cited by 233 · see citing works
Presynaptic nicotinic receptors modulating dopamine release in the rat striatum
Wonnacott, S., Kaiser, S., Mogg, A., Soliakov, L., & Jones, I. W. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00005-4 · Cited by 232 · see citing works
Gotti, C., Guiducci, S., Tedesco, V., Corbioli, S., Zanetti, L., Moretti, M., Zanardi, A., Rimondini, R., Mugnaini, M., Clementi, F., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5095-09.2010 · Cited by 226 · see citing works
Self-citationSalas, R., Pieri, F., & De Biasi, M. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1939-04.2004 · Cited by 226 · see citing works
The Role of Nicotine in Smoking: A Dual-Reinforcement Model
Caggiula, A. R., Donny, E. C., Palmatier, M. I., Liu, X., Chaudhri, N., & Sved, A. F. (2008) · Nebraska Symposium on Motivation · doi:10.1007/978-0-387-78748-0_6 · Cited by 226 · see citing works
Staley, J. K., Krishnan-Sarin, S., Cosgrove, K. P., Krantzler, E., Frohlich, E., Perry, E., Dubin, J. A., Estok, K., Brenner, E., Baldwin, R. M., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0546-06.2006 · Cited by 223 · see citing works
“Because the reinforcing properties of nicotine have been linked specifically to nAChRs that contain the 2 subunit ( 2*-nAChRs) (Picciotto et al., 1998), an understanding of the adaptive changes in 2*-nAChR number during acute abstinence and their relationship to behavioral correlates of tobacco…”
BackgroundSelf-citationPicciotto, M. R., Caldarone, B. J., Brunzell, D. H., Zachariou, V., Stevens, T. R., & King, S. L. (2001) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(01)00161-9 · Cited by 221 · see citing works
Self-citationGrubb, M. S., Rossi, F. M., Changeux, J.-P., & Thompson, I. D. (2003) · Neuron · doi:10.1016/s0896-6273(03)00789-x · Cited by 208 · see citing works
Self-citationNicotinic Modulation of Glutamate and GABA Synaptic Transmission in Hippocampal Neurons
RADCLIFFE, K. A., FISHER, J. L., GRAY, R., & DANI, J. A. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb11332.x · Cited by 205 · see citing works
Walters, C. L., Brown, S., Changeux, J.-P., Martin, B., & Damaj, M. I. (2006) · Psychopharmacology · doi:10.1007/s00213-005-0295-x · Cited by 206 · see citing works
Self-citationChronic Nicotine Exposure Upregulates Nicotinic Receptors by a Novel Mechanism
Vallejo, Y. F. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.5240-04.2005 · Cited by 201 · see citing works
GLP-1 acts on habenular avoidance circuits to control nicotine intake
Tuesta, L. M., Chen, Z., Duncan, A., Fowler, C. D., Ishikawa, M., Lee, B. R., Liu, X.-A., Lu, Q., Cameron, M., Hayes, M. R., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4540 · Cited by 200 · see citing works
Tribollet, E., Bertrand, D., Marguerat, A., & Raggenbass, M. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.09.028 · Cited by 199 · see citing works
Pidoplichko, V. I., Noguchi, J., Areola, O. O., Liang, Y., Peterson, J., Zhang, T., & Dani, J. A. (2004) · Learning & Memory · doi:10.1101/lm.70004 · Cited by 196 · see citing works
Nashmi, R., Dickinson, M. E., McKinney, S., Jareb, M., Labarca, C., Fraser, S. E., & Lester, H. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-37-11554.2003 · Cited by 188 · see citing works
Wang, F., Nelson, M. E., Kuryatov, A., Olale, F., Cooper, J., Keyser, K., & Lindstrom, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.44.28721 · Cited by 187 · see citing works
Regulation of synaptic transmission and plasticity by neuronal nicotinic acetylcholine receptors
McKay, B. E., Placzek, A. N., & Dani, J. A. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.07.001 · Cited by 181 · see citing works
Labarca, C., Schwarz, J., Deshpande, P., Schwarz, S., Nowak, M. W., Fonck, C., Nashmi, R., Kofuji, P., Dang, H., Shi, W., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.041582598 · Cited by 177 · see citing works
Nicotinic receptors in human brain: topography and pathology
Court, J. A., Martin-Ruiz, C., Graham, A., & Perry, E. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00110-1 · Cited by 180 · see citing works
Biological Aspects of the Link between Smoking and Depression
Quattrocki, E., Baird, A., & Yurgelun-Todd, D. (2000) · Harvard Review of Psychiatry · doi:10.1080/hrp_8.3.99 · Cited by 176 · see citing works
Rollema, H., Shrikhande, A., Ward, K., Tingley III, F., Coe, J., O'Neill, B., Tseng, E., Wang, E., Mather, R., Hurst, R., et al. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00682.x · Cited by 162 · see citing works
McGranahan, T. M., Patzlaff, N. E., Grady, S. R., Heinemann, S. F., & Booker, T. K. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0937-11.2011 · Cited by 165 · see citing works
Exley, R., Maubourguet, N., David, V., Eddine, R., Evrard, A., Pons, S., Marti, F., Threlfell, S., Cazala, P., McIntosh, J. M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103000108 · Cited by 159 · see citing works
Cosgrove, K. P., Batis, J., Bois, F., Maciejewski, P. K., Esterlis, I., Kloczynski, T., Stiklus, S., Krishnan-Sarin, S., O’Malley, S., Perry, E., et al. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.41 · Cited by 159 · see citing works
The role of the habenula in drug addiction
Velasquez, K. M., Molfese, D. L., & Salas, R. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00174 · Cited by 155 · see citing works
Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement
Tolu, S., Eddine, R., Marti, F., David, V, Graupner, M., Pons, S., Baudonnat, M., Husson, M., Besson, M., Reperant, C., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.83 · Cited by 151 · see citing works
Self-citationMechanisms of Nicotine Addiction
Picciotto, M. R., & Kenny, P. J. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a039610 · Cited by 157 · see citing works
Self-citationJackson, K. J., Marks, M. J., Vann, R. E., Chen, X., Gamage, T. F., Warner, J. A., & Damaj, M. I. (2010) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.165738 · Cited by 156 · see citing works
Grady, S. R., Meinerz, N. M., Cao, J., Reynolds, A. M., Picciotto, M. R., Changeux, J., McIntosh, J. M., Marks, M. J., & Collins, A. C. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00019.x · Cited by 156 · see citing works
Localization of nAChR subunit mRNAs in the brain of Macaca mulatta
Han, Z., Le Novère, N., Zoli, M., Hill, J. A., Champtiaux, N., & Changeux, J. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00262.x · Cited by 156 · see citing works
Self-citationThe habenulo-interpeduncular pathway in nicotine aversion and withdrawal
Antolin-Fontes, B., Ables, J. L., Görlich, A., & Ibañez-Tallon, I. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.11.019 · Cited by 154 · see citing works
Learning from Action: Reconsidering Movement Signaling in Midbrain Dopamine Neuron Activity
Coddington, L. T., & Dudman, J. T. (2019) · Neuron · doi:10.1016/j.neuron.2019.08.036 · Cited by 150 · see citing works
Levin, E. D., Lawrence, S. S., Petro, A., Horton, K., Rezvani, A. H., Seidler, F. J., & Slotkin, T. A. (2007) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2007.02.002 · Cited by 147 · see citing works
Xiao, Y., Fan, H., Musachio, J. L., Wei, Z.-L., Chellappan, S. K., Kozikowski, A. P., & Kellar, K. J. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027318 · Cited by 141 · see citing works
Berrendero, F., Robledo, P., Trigo, J. M., Martín-García, E., & Maldonado, R. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.02.006 · Cited by 140 · see citing works
Zhu, J., & Reith, M. (2008) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152708786927877 · Cited by 140 · see citing works
Maskos, U. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.5 · Cited by 139 · see citing works
Foulds, J. (2006) · International Journal of Clinical Practice · doi:10.1111/j.1368-5031.2006.00955.x · Cited by 136 · see citing works
The Role of α6-Containing Nicotinic Acetylcholine Receptors in Nicotine Reward and Withdrawal
Jackson, K. J., McIntosh, J. M., Brunzell, D. H., Sanjakdar, S. S., & Damaj, M. I. (2009) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.155457 · Cited by 135 · see citing works
Conti, D. V., Lee, W., Li, D., Liu, J., Van Den Berg, D., Thomas, P. D., Bergen, A. W., Swan, G. E., Tyndale, R. F., Benowitz, N. L., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn181 · Cited by 136 · see citing works
Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety
Nguyen, C., Mondoloni, S., Le Borgne, T., Centeno, I., Come, M., Jehl, J., Solié, C., Reynolds, L. M., Durand-de Cuttoli, R., Tolu, S., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.06.013 · Cited by 136 · see citing works
Ferrari, R., Le Novère, N., Picciotto, M. R., Changeux, J. P., & Zoli, M. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2001.02009.x · Cited by 132 · see citing works
Self-citationFowler, C. D., Arends, M. A., & Kenny, P. J. (2008) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32830c360e · Cited by 131 · see citing works
Drenan, R. M., Grady, S. R., Steele, A. D., McKinney, S., Patzlaff, N. E., McIntosh, J. M., Marks, M. J., Miwa, J. M., & Lester, H. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2056-10.2010 · Cited by 127 · see citing works
Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits
Mansvelder, H. D., Mertz, M., & Role, L. W. (2009) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2009.01.007 · Cited by 126 · see citing works
Role of nicotinic acetylcholine receptors in regulating dopamine neuron activity
Faure, P., Tolu, S., Valverde, S., & Naudé, J. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.05.040 · Cited by 125 · see citing works
Common aspects of the action of nicotine and other drugs of abuse
Picciotto, M. R. (1998) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(98)00074-x · Cited by 117 · see citing works
Self-citationElucidating the role of genetic factors in smoking behavior and nicotine dependence
Lerman, C., & Berrettini, W. (2003) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10003 · Cited by 114 · see citing works
Laviolette, S. R., & van der Kooy, D. (2003) · Psychopharmacology · doi:10.1007/s00213-002-1317-6 · Cited by 113 · see citing works
Arroyo-Jiménez, M. D. M., Bourgeois, J.-P., Marubio, L. M., Le Sourd, A.-M., Ottersen, O. P., Rinvik, E., Fairén, A., & Changeux, J.-P. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-15-06475.1999 · Cited by 110 · see citing works
Self-citationAlterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors
Ballesteros-Yáñez, I., Benavides-Piccione, R., Bourgeois, J.-P., Changeux, J.-P., & DeFelipe, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006269107 · Cited by 96 · see citing works
Self-citation
- Authors
- Picciotto, M. R., Zoli, M., Rimondini, R., Léna, C., Marubio, L. M., Pich, E. M., Fuxe, K., & Changeux, J.-P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Karolinska Institutet (SE)
- Venue
- Nature
- Published
- 1998-01
- Volume
- 391
- Issue
- 6663
- Pages
- 173-177
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1571140265
- Cited by
- 1,320
- References
- 29
- Citations by year
- 2026: 12 · 2025: 23 · 2024: 14 · 2023: 29 · 2022: 24 · 2021: 22 · 2020: 43 · 2019: 23 · 2018: 36 · 2017: 41 · 2016: 35 · 2015: 51 · 2014: 53 · 2013: 71 · 2012: 54
- FWCI
- 19.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine, nicotinic acetylcholine receptors, beta2 subunit, dopamine release, mesolimbic system, ventral striatum, dopaminergic neurons, self-administration, drug reinforcement
- MeSH terms
- Acetylcholine, Animals, Binding Sites, Carrier Proteins, Cocaine, Conditioning, Operant, Dopamine, Homovanillic Acid, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Inbred DBA, Motor Activity, Nerve Tissue Proteins, Nicotine, Nucleus Accumbens, Receptors, Nicotinic, Substantia Nigra, 3,4-Dihydroxyphenylacetic Acid, Second Messenger Systems, Microdialysis, Ventral Tegmental Area, Mice, Knockout, Patch-Clamp Techniques, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins, Mice, In Vitro Techniques
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
