ArticleMolecular psychiatry2014
Nicotine consumption is regulated by a human polymorphism in dopamine neurons.
Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.
- The Shared Genetic Architectures Between Lung Cancer and Multiple Polygenic Phenotypes in Genome-Wide Association Studies.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Pooled it
- Smoking Cessation Pharmacotherapy Based on Genetically-Informed Biomarkers: What is the Evidence?Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Pooled it
- Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Trial
- Response to Transdermal Selegiline Smoking Cessation Therapy and Markers in the 15q24 Chromosomal Region.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2015Trial
- Dual E-Cigarette Users Show Nicotine Addiction Risk Alleles and Nuclear Abnormalities in Oral Epithelial Cells.Advances in respiratory medicine · 2026Article
- The alpha7 nicotinic acetylcholine receptor mediates network dysfunction in a mouse model of local amyloid pathology.Molecular psychiatry · 2026Article
- A Cre-dependent lentiviral vector for neuron subtype-specific expression of large proteins.FEBS letters · 2026Article
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- The influence of CHRNA5 and D398N missense variation on social and emotional behaviors in rodents and humans.Translational psychiatry · 2025Article
- Adolescent isolation disrupts medial amygdala and ventral tegmental area maturation and sex-specifically dysregulates transcriptional responses to cocaine and stress.Neuropharmacology · 2025Article
- Design and validation of novel brain-penetrant HCN channel inhibitors to ameliorate social stress-induced susceptible phenotype.Molecular psychiatry · 2025Article
- Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors.Nature communications · 2025Article
- Arsenic and vanadium co-exposure induced cerebellar neurotoxicity: aggravates apoptosis, inflammation, oxidative stress, and locomotor deficits in juvenile BALB/c mice.Anatomy & cell biology · 2025Article
- Article
- "Unraveling the role ofReceptors (Basel, Switzerland) · 2025Article
- Nicotine and neuronal nicotinic acetylcholine receptors: unraveling the mechanisms of nicotine addiction.Frontiers in neuroscience · 2025Review
- Distinct Chrna5 mutations link excessive alcohol use to types I/II vulnerability profiles and IPN GABAergic neurons.Translational psychiatry · 2024Article
- Individualistic reward-seeking strategies that predict response to nicotine emerge among isogenic male mice living in a micro-society.PLoS biology · 2024Article
- Smoking-Related Increases in Alcohol Outcomes and Preliminary Evidence for the Protective Effect of a Functional Nicotine Receptor Gene (CHRNA5) Variant on Alcohol Consumption in Individuals Without Alcohol Use Disorder.The international journal of neuropsychopharmacology · 2024Article
- The association of genetic polymorphisms within the dopaminergic system with nicotine dependence: A narrative review.Heliyon · 2024Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Smoking is the most important preventable cause of morbidity and mortality worldwide. Recent genome-wide association studies highlighted a human haplotype on chromosome 15 underlying the risk for tobacco dependence and lung cancer. Several polymorphisms in the CHRNA3-CHRNA5-CHRNB4 cluster coding for the nicotinic acetylcholine receptor (nAChR) α3, α5 and β4 subunits were implicated. In mouse models, we define a key role in the control of sensitivity to nicotine for the α5 subunit in dopaminergic (DAergic) neurons of the ventral tegmental area (VTA). We first investigated the reinforcing effects of nicotine in drug-naive α5(-/-) mice using an acute intravenous nicotine self-administration task and ex vivo and in vivo electrophysiological recordings of nicotine-elicited DA cell activation. We designed lentiviral re-expression vectors to achieve targeted re-expression of wild-type or mutant α5 in the VTA, in general, or in DA neurons exclusively. Our results establish a crucial role for α5*-nAChRs in DAergic neurons. These receptors are key regulators that determine the minimum nicotine dose necessary for DA cell activation and thus nicotine reinforcement. Finally, we demonstrate that a single-nucleotide polymorphism, the non-synonymous α5 variant rs16969968, frequent in many human populations, exhibits a partial loss of function of the protein in vivo. This leads to increased nicotine consumption in the self-administration paradigm. We thus define a critical link between a human predisposition marker, its expression in DA neurons and nicotine intake.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.