A stereospecific chemosensory model suited to analyze nicotine perception, "liking" and sensory induced craving

• Applicant: Privatdozent Dr. Norbert Thürauf
• Subject Area: Biological Psychiatry
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 24615734

Nicotine not only represents the main addictive component of smoking but it also greatly contributes to the sensory properties of tobacco. 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. Thus, the stereospecificity of nicotine provides unique possibilities to investigate the influence of smoking history and former experienced nicotine consumption on nicotine perception, liking and on stimulus induced craving. Furthermore it provides an excellent tool to investigate the effects of conditioning processes during the process of smoking. Thus, the aims of our research applications are the identification of relevant central components of nicotine perception, liking, stimulus induced craving and conditioning mechanisms. It employs differential analysis of standard fMRI (bold effect), event-related-responses following chemical stimulation with nicotine enantiomers and fMRI guided MR-spectroscopy. Differences following sensory stimulation with R-(+)- and S-(-)-nicotine in non-smokers and in smokers will be analysed. Peripheral sensory blocking with mecamylamine will be used in order to investigate the role of trigeminal nicotinic input. fMRI guided MR-spectroscopy and the recording of sensory event-related-responses will be employed in order to compare different neural states - smoker, nicotine withdrawal, non-smoker - at the level of brain metabolites (MR-spectroscopy) and at the functional cortical level (event-related potentials). It is expected that a multi-center-study with a specific focus on the genetics of nicotine dependence (initiated by Winterer and Batra) will provide novel candidate genes in the near future. The functional characterization of carriers of such genetic variations could represent a specific goal for the second funding period.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1226: Nicotine: Molecular and Physiological Effects in the Central Nervous System (CNS)
• Major Instrumentation: Olfaktometer
• Instrumentation Group: 3231 MR-Tomographie-Systeme
• Participating Persons: Professor Dr. Stefan Bleich; Dr. Thilo Hammen; Professor Dr. Johannes Kornhuber