ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
α4β2 nicotinic acetylcholine receptors on dopaminergic neurons mediate nicotine reward and anxiety relief.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 4 of them syntheses that pooled it.
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The trial behind it
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
92 citing papers in PubMed, 4 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Genetic Analysis of Lung Cancer and the Germline Impact on Somatic Mutation Burden.Journal of the National Cancer Institute · 2022Pooled it
- Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?-A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Tobacco smoking and dopaminergic function in humans: a meta-analysis of molecular imaging studies.Psychopharmacology · 2019Pooled it
- Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence.Translational psychiatry · 2015Pooled it
- Recent cannabis exposure and acute nicotine effects: insights from randomized, double-blind, placebo-controlled intravenous nicotine studies.The international journal of neuropsychopharmacology · 2026Trial
- Effect of varenicline on aspects of inhibitory control in smokers.Psychopharmacology · 2014Trial
- Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Trial
- Toxicological and pharmacodynamic evaluation of Nixodine-S [(S)-6-Methylnicotine] relative to (S)-nicotine.Toxicology reports · 2026Article
- Therapeutic potential of varenicline in neuropsychiatric disorders: insights into its molecular mechanisms.Molecular biology reports · 2026Review
- Nicotine in Neurodegenerative and Neuropsychiatric Disorders: Mechanisms and Clinical Evidence.Neurochemical research · 2026Review
- Varenicline-mediated cholinergic activation through α4β2 nAChR inhibits microglial neuroinflammation and alleviates neuropathic pain and depression following spinal cord injury.Journal of translational medicine · 2026Article
- Complete nicotine biosynthesis reshapes the understanding of a classic alkaloid metabolic pathway.Frontiers in plant science · 2026Article
- Precise mapping of a snake venom phospholipase AToxicon : official journal of the International Society on Toxinology · 2025Article
- Article
- Enantiospecific Positive Allosteric Modulation of α4β2 Nicotinic Receptor Subtypes.ACS chemical neuroscience · 2025Article
- Characterization of a novel oronasal-restricted nicotine vaping self-administration model in mice.Neuropharmacology · 2025Article
- The Role of α7-Nicotinic Acetylcholine Receptors in the Pathophysiology and Treatment of Parkinson's Disease.International journal of molecular sciences · 2025Review
- Alcohol-induced liver injury is mediated via α4-containing nicotinic acetylcholine receptors expressed in hepatocytes.Alcohol, clinical & experimental research · 2025Article
- Article
- Nicotine and neuronal nicotinic acetylcholine receptors: unraveling the mechanisms of nicotine addiction.Frontiers in neuroscience · 2025Review
32 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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What OpenQuestion holds
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.