The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
4 2 Nicotinic Acetylcholine Receptors on Dopaminergic Neurons Mediate Nicotine Reward and Anxiety Relief
Open accessAbstract
Nicotine is the primary psychoactive substance in tobacco, and it exerts its effects by interaction with various subtypes of nicotinic acetylcholine receptors (nAChRs) in the brain. One of the major subtypes expressed in brain, the α4β2-nAChR, endogenously modulates neuronal excitability and thereby, modifies certain normal as well as nicotine-induced behaviors. Although α4-containing nAChRs are widely expressed across the brain, a major focus has been on their roles within midbrain dopaminergic regions involved in drug addiction, mental illness, and movement control in humans. We developed a unique model system to examine the role of α4-nAChRs within dopaminergic neurons by a targeted genetic deletion of the α4 subunit from dopaminergic neurons in mice. The loss α4 mRNA and α4β2-nAChRs from dopaminergic neurons was confirmed, as well as selective loss of α4β2-nAChR function from dopaminergic but not GABAergic neurons. Two behaviors central to nicotine dependence, reward and anxiety relief, were examined. α4-nAChRs specifically on dopaminergic neurons were demonstrated to be necessary for nicotine reward as measured by nicotine place preference, but not for another drug of addiction, cocaine. α4-nAChRs are necessary for the anxiolytic effects of nicotine in the elevated plus maze, and elimination of α4β2-nAChRs specifically from dopaminergic neurons decreased sensitivity to the anxiolytic effects of nicotine. Deletion of α4-nAChRs specifically from dopaminergic neurons also increased sensitivity to nicotine-induced locomotor depression; however, nicotine-induced hypothermia was unaffected. This is the first work to develop a dopaminergic specific deletion of a nAChR subunit and examine resulting changes in nicotine-related behaviors.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Similarly, knockout of the α4 subunit abolishes intracerebroventricular (i.c.v.) selfadministration of nicotine, consistent with evidence that α4/β2 Ã nAChRs are required for depolarization of DA neurons in the VTA (Exley et al. 2011;McGranahan et al. 2011).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as McGranahan et al. 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In contrast, in mice with constitutive knockout of the α6 subunit, intra-VTA selfadministration of nicotine is not disrupted, whereas α4 Ã nAChRs are necessaryand sufficient for both intra-VTA self-administration, as well as nicotine-induced increases in firing of DA neurons (Exley et al. 2011;McGranahan et al. 2011).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as McGranahan et al. 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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 McGranahan et al., 2011
Experimental — accuracy not yet measuredIn the citing paper
“mice lacking β2* nAChRs in dopamine neurons of the VTA lack anxiolytic responses to nicotine and are insensitive to nicotine reward (McGranahan et al., 2011)”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as McGranahan et al., 2011
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 McGranahan et al., 2011
In the citing paper
“McGranahan, Patzlaff, Grady, Heinemann, and Booker (2011) found that selective elimination of α4β2 nAChRs located on dopaminergic neurons reversed the anxiolytic effects of nicotine.”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as McGranahan et al. (2011)
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Projections of Global Mortality and Burden of Disease from 2002 to 2030
Mathers, C. D., & Loncar, D. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030442 · Cited by 11,386
International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels
Catterall, W. A., Chandy, K. G., Clapham, D. E., Gutman, G. A., Hofmann, F., Harmar, A. J., Abernethy, D. R., & Spedding, M. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.4.5 · Cited by 7,126
Di Chiara, G., & Imperato, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5274 · Cited by 4,733
Krishnan, V., Han, M.-H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., LaPlant, Q., Graham, A., Lutter, M., Lagace, D. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.09.018 · Cited by 2,307
Is there a common molecular pathway for addiction?
Nestler, E. J. (2005) · Nature Neuroscience · doi:10.1038/nn1578 · Cited by 1,388
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
Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1.
Sauer, B., & Henderson, N. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5166 · Cited by 1,213
Pierce, R. C., & Kumaresan, V. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.04.016 · Cited by 913
Neuronal nicotinic receptors in the human brain
Paterson, D., & Nordberg, A. K. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00045-3 · Cited by 792
Corrigall, W. A., Coen, K. M., & Adamson, K. L. (1994) · Brain Research · doi:10.1016/0006-8993(94)90401-4 · Cited by 740
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
Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics
Kim, T.-I., McCall, J. G., Jung, Y. H., Huang, X., Siuda, E. R., Li, Y., Song, J., Song, Y. M., Pao, H. A., Kim, R.-H., et al. (2013) · Science · doi:10.1126/science.1232437 · Cited by 1,174
Moylan, S., Jacka, F. N., Pasco, J. A., & Berk, M. (2013) · Brain and Behavior · doi:10.1002/brb3.137 · Cited by 186
Molecular Mechanisms Underlying Behaviors Related to Nicotine AddictionPreprint
Picciotto, M. R., & Kenny, P. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012112 · Cited by 186
Mechanisms of Nicotine Addiction
Picciotto, M. R., & Kenny, P. J. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a039610 · Cited by 161
Metadata
- Authors
- McGranahan, T. M., Patzlaff, N. E., Grady, S. R., Heinemann, S. F., & Booker, T. K.
- Affiliations
- Salk Institute for Biological Studies (US)
- University of Colorado Boulder (US)
- ORCID
- McGranahan, T. M.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-07-27
- Volume
- 31
- Issue
- 30
- Pages
- 10891-10902
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3539812
- OpenAlex
- W1973295491
- Cited by
- 165
- References
- 60
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 20 · 2023: 12 · 2022: 4 · 2021: 9 · 2020: 12 · 2019: 5 · 2018: 3 · 2017: 9 · 2016: 10 · 2015: 17 · 2014: 14 · 2013: 21 · 2012: 9
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA13018, R01AA013018)
- National Institute on Drug Abuse (DA018247, R01DA018247, DA012242, R01DA003194, DA003194, R01DA012242)
- National Institute of Neurological Disorders and Stroke (NS10830, F32NS010830)
- 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
- nicotinic acetylcholine receptors, alpha4beta2 nAChR, dopaminergic neurons, nicotine reward, nicotine dependence, midbrain dopaminergic system, cocaine reward
- MeSH terms
- Analysis of Variance, Animals, Anxiety, Behavior, Animal, Body Temperature, Conditioning, Operant, Disease Models, Animal, Dopamine, Female, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Male, Mesencephalon, Mice, Inbred C57BL, Neurons, Nicotine, Protein Binding, Pyridines, Receptors, Nicotinic, Reward, Synaptosomes, Tritium, Mice, Knockout, Nicotinic Agonists, Bridged Bicyclo Compounds, Heterocyclic, Dopamine Plasma Membrane Transport Proteins, 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
