ArticleMolecular pharmacology2012
Nicotine persistently activates ventral tegmental area dopaminergic neurons via nicotinic acetylcholine receptors containing α4 and α6 subunits.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
74 citing papers in PubMed, 120 citations in OpenAlex.
- Nicotine reduces discrimination between threat and safety in the hippocampus, nucleus accumbens and amygdala.Translational psychiatry · 2024Trial
- Cool but not harmless: synthetic cooling agents enhance nicotine reinforcement via the mesolimbic dopamine system.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Synthetic cooling agents enhance nicotine reinforcement and mesolimbic dopamine signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Beyond dopamine: Broader neuromodulatory contributions in sign- and goal-tracking.Psychopharmacology · 2026Review
- Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors.Nature communications · 2025Article
- "Unraveling the role ofReceptors (Basel, Switzerland) · 2025Article
- Transcriptomic Dysregulation in Animal Models of Attention-Deficit Hyperactivity Disorder and Nicotine Dependence Suggests Shared Neural Mechanisms.Brain and behavior · 2025Article
- Nicotine and neuronal nicotinic acetylcholine receptors: unraveling the mechanisms of nicotine addiction.Frontiers in neuroscience · 2025Review
- The Impact of High or Low Doses of Nicotine in a Mouse Model of Vapor Self-Administration.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Association between Single Nucleotide Polymorphisms in Monoamine Oxidase and the Severity of Addiction to Betel Quid.Current issues in molecular biology · 2024Article
- New medications development for smoking cessation.Addiction neuroscience · 2023Article
- Cholinergic depolarization recruits a persistent CaJournal of neurophysiology · 2023Article
- Chemical Flavorants in Vaping Products Alter Neurobiology in a Sex-Dependent Manner to Promote Vaping-Related Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Betel quid: New insights into an ancient addiction.Addiction biology · 2022Article
- Interactions between the Nicotinic and Endocannabinoid Receptors at the Plasma Membrane.Membranes · 2022Review
- Morphine Exposure Reduces Nicotine-Induced Upregulation of Nicotinic Receptors and Decreases Volitional Nicotine Intake in a Mouse Model.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Article
- The incentive amplifying effects of nicotine: Roles in alcohol seeking and consumption.Advances in pharmacology (San Diego, Calif.) · 2022Review
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- New Insights in the Involvement of the Endocannabinoid System and Natural Cannabinoids in Nicotine Dependence.International journal of molecular sciences · 2021Review
- Unbalanced Regulation of α7 nAChRs by Ly6h and NACHO Contributes to Neurotoxicity in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Nicotine is reinforcing because it activates dopaminergic (DAergic) neurons within the ventral tegmental area (VTA) of the brain's mesocorticolimbic reward circuitry. This increase in activity can occur for a period of several minutes up to an hour and is thought to be a critical component of nicotine dependence. However, nicotine concentrations that are routinely self-administered by smokers are predicted to desensitize high-affinity α4β2 neuronal nicotinic acetylcholine receptors (nAChRs) in seconds. Thus, how physiologically relevant nicotine concentrations persistently activate VTA DAergic neurons is unknown. Here we show that nicotine can directly and robustly increase the firing frequency of VTA DAergic neurons for several minutes. In mouse midbrain slices, 300 nM nicotine elicited a persistent inward current in VTA DAergic neurons that was blocked by α-conotoxin MII[H9A;L15A], a selective antagonist of nAChRs containing the α6 subunit. α-conotoxin MII[H9A;L15A] also significantly reduced the long-lasting increase in DAergic neuronal activity produced by low concentrations of nicotine. In addition, nicotine failed to significantly activate VTA DAergic neurons in mice that did not express either α4 or α6 nAChR subunits. Conversely, selective activation of nAChRs containing the α4 subunit in knock-in mice expressing a hypersensitive version of these receptors yielded a biphasic response to nicotine consisting of an acute desensitizing increase in firing frequency followed by a sustained increase that lasted several minutes and was sensitive to α-conotoxin MII[H9A;L15A]. These data indicate that nicotine persistently activates VTA DAergic neurons via nAChRs containing α4 and α6 subunits.
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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.