Abstract
Nicotine presented to the nasal cavity at low concentrations evokes ‘odorous’ sensations, and at higher concentrations ‘burning’ and ‘stinging’ sensations. A study in smokers and nonsmokers provided evidence of a relationship between the experience with the pharmacological action of S-(−)-nicotine and the perceived pleasantness/unpleasantness following nasal stimulation with S-(−)-nicotine. Mecamylamine, a nicotinic acetylcholine-receptor-(nAch-R) antagonist, was able to block painful responses following chemical stimulation of the human tongue and to block responses from the rat's ethmoidal nerve. The aim of our study in humans was to investigate the effects of mecamylamine on the olfactory and the trigeminal chemoreception of nicotine enantiomers. In order to achieve this aim, we determined—before and after mecamylamine—(1) detection thresholds, trigeminal thresholds, and intensity estimates (stimulus intensity) and (2) recorded the negative mucosal potential (NMP) following nasal stimulation with nicotine in a placebo-controlled double blind study (n=15). CO2 was used as a trigeminal and H2S as an olfactory control stimulus. Mecamylamine significantly increased trigeminal thresholds of S-(−)-nicotine and reduced intensity estimates and NMPs following stimulation with nicotine enantiomers, whereas mecamylamine did not influence NMPs and trigeminal intensity estimates following stimulation with CO2. In contrast, mecamylamine did neither influence detection thresholds nor olfactory intensity estimates following stimulation with olfactory nicotine concentrations. These results demonstrate that the trigeminal nasal chemoreception of nicotine enantiomers, in contrast to CO2, is mediated by nAch-Receptors and give evidence that the olfactory chemoreception of nicotine is independent from peripheral nAch-Receptors.
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Acknowledgements
The research described in this article was supported by Philip Morris USA Inc. (Philip Morris External Research Program/Fellowship). We thank Susanne Schroeder-Thuerauf (Department of Languages for Special Purposes, University of Erlangen-Nürnberg, Germany) and Bruce Bryant (Monell Chemical Senses Center, Philadelphia, PA USA) for helpful suggestions during the preparation of the manuscript and Elfriede Hoh (Department of Psychiatry and Psychotherapy, University of Erlangen-Nürnberg) for assistance during the experiments.
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Thuerauf, N., Markovic, K., Braun, G. et al. The Influence of Mecamylamine on Trigeminal and Olfactory Chemoreception of Nicotine. Neuropsychopharmacol 31, 450–461 (2006). https://doi.org/10.1038/sj.npp.1300842
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DOI: https://doi.org/10.1038/sj.npp.1300842
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