A stereospecific chemosensory model suited to analyze nicotine perception, "liking" and sensory induced craving
Final Report Abstract
A human stereospecific sensory model for nicotine dependency was developed based on the fact that (1) smokers experience the sensory properties of S-nicotine during smoking, but both – smokers and non-smokers – are naive to the sensory properties of R-nicotine and based on the fact that (2) stereoisomers have identical physicochemical properties. After the characterization of the possible confounders age, gender, stimulation site we tested balanced groups of smokers, smokers on withdrawal and non-smokers in our stereospecific sensory model employing the recording of event-related potentials and fMRI-imaging. ERPs / Psychophysics: In overall olfactory and in overall trigeminal stimuli we found significantly higher hedonic estimates and significantly lower p2-amplitudes for smokers compared to non-smokers On withdrawal, overall olfactory stimuli coincided with significantly shorter p2-latencies. A weaker effect of the status ‘withdrawal’ on latencies could be observed for the overall trigeminal stimuli. We concluded that nicotine addiction is associated with a more pleasantly-tuned hedonic evaluation system for chemosensory stimuli. Nicotine deprivation of three days did not reverse the subjective hedonic evaluation, but it normalized the cortical responses in the EEG for trigeminal stimuli. Hedonic evaluation and grouping of olfactory stimuli are accelerated during nicotine withdrawal. A more positively tuned hedonic system in nicotine addiction could be of paramount clinical importance since an altered hedonic system could also increase the risk of developing other addictive disorders and disorders related to disturbances in food intake causing obesity. Thus confirmatory studies employing more odors and stimuli of other sensory modalities are requested. Explorative analyses of the relationship between perceived odors and perceived craving in smokers and smokers on withdrawal point to a modulating effect of odors on perceived craving. This preliminary finding needs confirmation with carefully designed studies employing a wider range of odorants and different olfactory exposure techniques. fMRT: Our most interesting finding with respect to nicotine perception was the activation of the trigeminal system in lower i.e. olfactory concentrations. Surprisingly we found activation of SII for the weaker R-nicotine enantiomer (weaker means lower trigeminal strength) at low stimulus concentrations. This finding clearly extends the results of Albrecht et al. Comparing the activation pattern of both nicotine enantiomers we found significant differences between smokers and non-smokers with activation of regions correlating with craving for S-nicotine (amygdala, anteriores cingulum, nucleus accumbens, hippocampus). Analyzing perceived craving in smokers and smokers on withdrawal we found significant correlations with the insula, the prefrontal cortex and as a tendency the nucleus accumbens. In addition, we found for the first time evidence for a role of the left inferior temporal gyrus (visual memory functions) and the left cingulum (negative emotions) for the perception of craving. fMRI guided MR-spectroscopy: Earlier 1H-MRS studies of the human brain have implemented the single-voxel technique (SVS), acquiring a single spectrum from a definite volume of tissue as an integral. We have implemented T2-weighted Turbo- Spin-Echo (TSE) images in three orthogonal planes as localizers with hippocampus and cingulum as areas of interest. In our study in smokers, smokers on withdrawal and non-smokers we found increased glutamate and glutamine in the cingulum when smokers were compared to non-smokers. In smokers on withdrawal a normalization of both metabolites was noticed when compared to the smoking status. We concluded that smoking interferes directly or indirectly with the glutamate/glutamine circuit in the cingulum. Nicotine deprivation of three days leads to some extent to a normalization of both metabolites.
Publications
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Good News for the Elderly: Olfactory Pleasure increases at Later Stages of the Life Span, J Gerontol A Biol Sci Med Sci 62 (2007) 1287-1293
Markovic K, Reulbach U, Vassiliadu A, Lunkenheimer J, Lunkenheimer B, Spannenberger R, Thürauf N
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Olfactory lateralization: Odor intensity but not the hedonic estimation is lateralized, Neurosci Lett 438 (2008) 228-232
Thürauf N, Gossler A, Lunkenheimer J, Lunkenheimer B, Reulbach U, Markovic K
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Emotional reactivity to odors: olfactory sensitivity and the span of emotional evaluation separate the genders, Neurosci Lett 456 (2009) 74-79
Thürauf N, Reulbach U, Vassiliadu A, Lunkenheimer J, Lunkenheimer B, Spannenberger R, Markovic K
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Multi-voxel magnetic resonance spectroscopy of cerebral metabolites in healthy adults at 3 Tesla, Acad Radiol 16 (2009) 1493-1501
Doelken MT, Mennecke A, Stadlbauer A, Kloska S, Struffert T, Engelhorn T, Thürauf N, Doerfler A, Stefan H, Hammen T
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Nikotin: Molekulare und physiologische Effekte im Zentralnervensystem. Ein stereospezifisches Modell zur Analyse der Nikotinperzeption, liking und sensorisch induziertem Craving. Doctoral thesis. University of Bamberg Press Bamberg 2010. ISBN: 978-3-923507-69-6
Andrea Gossler
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The Relation between Depression, Anhedonia and Olfactory Hedonic Estimates-A Pilot Study in Major Depression, Neurosci Lett. 2010 Mar 8;471(3):139-43
Clepce M, Gossler A, Reich K, Kornhuber J, Thürauf N
