ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Chronic nicotine cell specifically upregulates functional alpha 4* nicotinic receptors: basis for both tolerance in midbrain and enhanced long-term potentiation in perforant path.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers.
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Who cites it
173 citing papers in PubMed, 267 citations in OpenAlex.
- Acute nicotine differentially impacts anticipatory valence- and magnitude-related striatal activity.Biological psychiatry · 2013Trial
- Chronic exposure to nicotine is associated with reduced reward-related activity in the striatum but not the midbrain.Biological psychiatry · 2012Trial
- Synthetic cooling agents enhance nicotine reinforcement and mesolimbic dopamine signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- Continuous Nicotine Monitors for Personal Nicotine Pharmacokinetics: A Receptor-Aware Research Agenda.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2025Review
- Nicotine Attenuates Molecular Signalings in the BTBR TMolecular neurobiology · 2025Article
- The influence of high-fat diet on nicotine vapor self-administration, neuronal excitability, and leptin levels in adult mice.Physiology & behavior · 2025Article
- Expression of sensitized β2 nAChR subunits in VTA neurons enhances intravenous nicotine self-administration in male rats.Neuropharmacology · 2024Article
- Age-dependent effects of vaping on the prefrontal cortex, ventral tegmental area, and nucleus accumbens.Communications biology · 2024Article
- Does the time to nicotine dependence vary by internalizing symptoms for young people who use e-cigarettes? An analysis of the Population Assessment of Tobacco and Health (PATH) study, (Waves 1-5; 2013-2019).Addictive behaviors · 2024Article
- α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata.Acta pharmacologica Sinica · 2024Article
- Ameliorating effects of Acanthopanax koreanum extract and components on nicotine dependence and withdrawal symptoms.Addiction biology · 2024Article
- Article
- Neuronal nicotinic acetylcholine receptor antibodies in autoimmune central nervous system disorders.Frontiers in immunology · 2024Article
- The many enigmas of nicotine.Advances in pharmacology (San Diego, Calif.) · 2024Review
- CHRNA5 gene variation affects the response of VTA dopaminergic neurons during chronic nicotine exposure and withdrawal.Neuropharmacology · 2023Article
- Review
- Article
- Understanding the habenula: A major node in circuits regulating emotion and motivation.Pharmacological research · 2023Review
- 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
113 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Understanding effects of chronic nicotine requires identifying the neurons and synapses whose responses to nicotine itself, and to endogenous acetylcholine, are altered by continued exposure to the drug. To address this problem, we developed mice whose alpha4 nicotinic receptor subunits are replaced by normally functioning fluorescently tagged subunits, providing quantitative studies of receptor regulation at micrometer resolution. Chronic nicotine increased alpha4 fluorescence in several regions; among these, midbrain and hippocampus were assessed functionally. Although the midbrain dopaminergic system dominates reward pathways, chronic nicotine does not change alpha4* receptor levels in dopaminergic neurons of ventral tegmental area (VTA) or substantia nigra pars compacta. Instead, upregulated, functional alpha4* receptors localize to the GABAergic neurons of the VTA and substantia nigra pars reticulata. In consequence, GABAergic neurons from chronically nicotine-treated mice have a higher basal firing rate and respond more strongly to nicotine; because of the resulting increased inhibition, dopaminergic neurons have lower basal firing and decreased response to nicotine. In hippocampus, chronic exposure to nicotine also increases alpha4* fluorescence on glutamatergic axons of the medial perforant path. In hippocampal slices from chronically treated animals, acute exposure to nicotine during tetanic stimuli enhances induction of long-term potentiation in the medial perforant path, showing that the upregulated alpha4* receptors in this pathway are also functional. The pattern of cell-specific upregulation of functional alpha4* receptors therefore provides a possible explanation for two effects of chronic nicotine: sensitization of synaptic transmission in forebrain and tolerance of dopaminergic neuron firing in midbrain.
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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.