ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 79 citations in OpenAlex.
- Acute effects of inhaled menthol on cognitive effects of intravenous nicotine among young adult cigarette smokers.Addictive behaviors · 2021Trial
- Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers.Journal of psychopharmacology (Oxford, England) · 2018Trial
- Naltrexone, Naloxone, Morphine, and Fentanyl Pharmacologically Chaperone a Mutant μ-Opioid Receptor via an Endoplasmic Reticulum Exit Site-Dependent Pathway.Pharmacology research & perspectives · 2026Article
- Synthetic cooling agents enhance nicotine reinforcement and mesolimbic dopamine signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Effects of commercial unflavored and vanilla-flavored e-liquids on nicotine intake and withdrawal.bioRxiv : the preprint server for biology · 2026Article
- Chemosensory tobacco product toxicology part 2: toxicological testing, assays, and state of the science.Toxicological sciences : an official journal of the Society of Toxicology · 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
- Cold receptor TRPM8 as a target for migraine-associated pain and affective comorbidities.The journal of headache and pain · 2025Article
- Reinforcement and MAO-A inhibition in heated tobacco products: flavor and brand variations.Frontiers in psychiatry · 2025Article
- Gender Differences in Quit Rates in a Tobacco Cessation Program: In Search of Demographic, Socioeconomic, Health, or Behavioral Explanatory Mechanisms.Journal of biomedical and life sciences · 2025Article
- Lower Successful Quit Rate of Menthol Tobacco Users in a Tobacco Cessation Program: An Explanatory Analysis in Search of Potential Mechanisms.Global journal of cardiovascular diseases · 2025Article
- Trends in Smoking and Flavored Tobacco Use in California: Black-White Disparities, 2003-2023.Global journal of epidemiology and infectious disease · 2025Article
- Article
- Investigating the role of nicotinic acetylcholine receptors in menthol's effects in mice.Drug and alcohol dependence · 2024Article
- Article
- Neuronal nicotinic acetylcholine receptor antibodies in autoimmune central nervous system disorders.Frontiers in immunology · 2024Article
- 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
- 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 distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.Frontiers in molecular neuroscience · 2022Review
- Differences in Cognitive Task Performance, Reinforcement Enhancement, and Nicotine Dependence Between Menthol and Nonmenthol Cigarette Smokers.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway.
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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.