Specific Sensory Detection, Discrimination, and Hedonic Estimation of Nicotine Enantiomers in Smokers and Nonsmokers: Are There Limitations in Replacing the Sensory Components of Nicotine?

Abstract

The aim of this study was to investigate in smokers and nonsmokers (1) the olfactory and trigeminal detection of R(+)- and S(-)-nicotine and (2) the discrimination ability and hedonic estimation of nicotine enantiomers in olfactory and trigeminal concentrations. Thirty healthy male subjects (15 smokers, 15 nonsmokers) participated in the experiments. A randomized sequence of R(+)- and S(-)-nicotine stimuli (seven R(+)- and seven S(-)-nicotine stimuli) were introduced into the right nostril of the subjects using a Kobal-olfactometer. The subjects were instructed to group the stimuli into two categories (A and B). To test the role of the olfactory and the trigeminal system in this discrimination task, the authors studied the olfactory detection threshold for the "odorous" sensation and the trigeminal detection thresholds for the "burning" and "stinging" sensations. Nicotine enantiomers were presented at the individual "olfactory" and "trigeminal" concentration levels. The subjects estimated the hedonic properties using a bipolar visual analog scale (from "very unpleasant" to "very pleasant"). A statistical evaluation (t-test) revealed that the subjects were able to identify R(+)- and S(-)-nicotine at olfactory and trigeminal concentrations (p < or = 0.01, p < or = 0.001, respectively). At concentrations near the detection thresholds, i.e., clearly below subjective pain thresholds, smokers rated both nicotine stereoisomers to be significantly more pleasant than did nonsmokers (t-test, R(+)-nicotine: p < or = 0.05; S(-)-nicotine: p < or = 0.01). Increasing the concentrations to above trigeminal thresholds resulted in a difference in hedonic estimates. Smokers perceived the S(-)-isomer as being less unpleasant than nonsmokers at trigeminal concentrations (t-test, p < or = 0.001). This difference in perception might be explained by the smokers' experience with S(-)-nicotine, which is the natural nicotine enantiomer in tobacco.

The Influence of Mecamylamine on Trigeminal and Olfactory Chemoreception of Nicotine

“…Nicotine not only represents the main addictive component of smoking but it also greatly contributes to the sensory properties of tobacco (Laviolette and van der Kooy, 2004;Walker et al, 1996;Hummel et al, 1992a, b;Thuerauf et al, 1999Thuerauf et al, , 2000. The substance presented to the nasal cavity at low concentrations evokes 'odorous' sensations and at higher concentrations 'burning' and 'stinging' sensations, possibly mediated by nicotinic acetylcholine receptors (nAchR) (Walker et al, 1996;Thuerauf et al, 1999).…”

“…In contrast to the majority of other chemical compounds, nicotine activates the olfactory and the trigeminal system at relatively low concentrations (Hummel et al, 1992a, b). During the last decade stereospecific differences between nicotine enantiomers have been reported for the nasal trigeminal sensory system (Thuerauf et al, 1999(Thuerauf et al, , 2000Walker et al, 1996). S-(À)-nicotineFthe natural isomer of tobaccoFpossesses lower trigeminal thresholds and higher stimulus strength for the 'burning' and the 'stinging' sensation compared to R-( þ )-nicotine.…”

“…Smokers experience the sensory properties of S-(À)-nicotine during smoking but bothFsmokers and nonsmokersFare naïve to the sensory properties of R-( þ )-nicotine. Two studies in smokers and nonsmokers provided evidence of a relationship between the experience with the pharmacological action of S-(À)-nicotine and the hedonic rating (pleasantness/unpleasantness) (Hummel et al, 1992a;Thuerauf et al, 2000). Smokers perceived the S-(À)-isomer as being more pleasant (or less unpleasant) than nonsmokers.…”

“…The difference in hedonic estimates has been explained by smokers' experience with the actions of S-(À)-nicotine pointing strongly to a conditioning mechanism between the sensory stimulus and the pleasant pharmacological actions of S-(À)-nicotine. In one of the two studies in smokers and nonsmokers, nitrogen was used as carrier gas for nicotine enantiomers and precise concentration measurements by means of a UV-detection method were conducted (Thuerauf et al, 2000). This study clearly revealed (1) that the different hedonic estimates of smokers and nonsmokers reflect hedonic differences in nicotine stereoisomers and not differences due to compounds formed by degradation and (2) that the differences in hedonic estimates appear exclusively when nicotine stimulus concentrations that activate the trigeminal system were used.…”

“…This study clearly revealed (1) that the different hedonic estimates of smokers and nonsmokers reflect hedonic differences in nicotine stereoisomers and not differences due to compounds formed by degradation and (2) that the differences in hedonic estimates appear exclusively when nicotine stimulus concentrations that activate the trigeminal system were used. It is well known that these stimulus concentrations are achieved during the process of cigarette smoking (Davies and Vaught, 1990;Thuerauf et al, 2000).…”