Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability
Abstract
Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.
Additional Information
© 2017 The Author(s). This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. Received 20 December 2016. Revised 28 March 2017. Accepted 1 April 2017. Accepted article preview online 12 April 2017. Funding: National Institutes of Health (NIH) (DA040047, DA033721, DA036061, DA037161, and DA037743). We declare no conflict of interest.Attached Files
Published - npp201772a.pdf
Supplemental Material - npp201772x1.docx
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Additional details
- PMCID
- PMC5645749
- Eprint ID
- 76644
- Resolver ID
- CaltechAUTHORS:20170418-150133796
- DA040047
- NIH
- DA033721
- NIH
- DA036061
- NIH
- DA037161
- NIH
- DA037743
- NIH
- Created
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2017-04-19Created from EPrint's datestamp field
- Updated
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2022-03-28Created from EPrint's last_modified field