SPP 1226:  Nicotine: Molecular and Physiological Effects in the Central Nervous System (CNS)

• Subject Area: Medicine
• Term: from 2006 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 18037864

One third of adults worldwide smoke and in the year 2000, smoking caused about 2,5 millions of deaths in the industrialised nations (19 percent mortality in adults). Therefore, an improved understanding of the central nervous effects of nicotine would be highly desirable from a medical as well as an economic point of view. In the biopsychological model of nicotine dependence, it is thought that the addiction to nicotine is to some considerable extent rooted in the neurobiological disposition of a person (heritability is approximately 50 percent). In this model, nicotine dependence is a clinically heterogenous and complex-polygenic disorder in exchange with environmental factors. Accordingly, it will not be sufficient to simply compare genes between smokers and non-smokers, but to take into account factors such personality, individual "craving", cognitive status, endocrinological changes including stress hormones as well as receptor binding and functional changes in the brain.
The Priority Programme has established a network comprising basic and clinical research to address questions about:
(1) molecular genetic mechanisms involved in human nicotine dependence including mechanisms of genetic-environmental interactions,
(2) clinical phenotyping of large multicentre samples in the general population as well as in neuropsychiatric patients including withdrawal-related changes and relapse risk factors,
(3) functional analysis of physiological effects of nicotine and nicotine withdrawal on the brain based on neuroimaging, electrophysiologic and endocrinological analysis.
The Priority Programme encompasses 16 subprojects and includes projects on animal models for the identification of genetic risk factors, large multicentre database projects with standardised data-acquisition in the general population and relevant clinical populations, statistical projects developing methods to handle complex biological and disease trajectory data as well as neuroimaging and physiological projects studying humans and animal models.

• DFG Programme: Priority Programmes
• International Connection: Switzerland

Projects

• A multimodal genomic imaging study on the effects of nicotine and nicotine withdrawal on brain circuits using simultaneous EEG/EMG, fMRI and PET (Applicants Gründer, Gerhard ;  Shah, Ph.D., Nadim Jon ;  Winterer, Georg )
• A stereospecific chemosensory model suited to analyze nicotine perception, "liking" and sensory induced craving (Applicant Thürauf, Norbert )
• Analysis of novel nicotine dependence related candidate genes identified through a genome-wide association study (Applicants Dahmen, Norbert ;  Gal, Andreas ;  Rujescu, Dan ;  Wichmann, Heinz-Erich )
• Dopamine metabolism in nicotine dependance: [18 F]FDOPA-PET and FMRI studies in smoking and detoxified subjects (Applicant Gründer, Gerhard )
• Effects of nicotine on social cognition and social stress in schizophrenia (Applicant Wölwer, Wolfgang )
• Functional Validation of Candidate Genes Deriving from Convergent Analysis of Gene Expression Profiling in Nicotine Self-Administering Animals and Genome Wide Association Studies in Smokers (Applicant Spanagel, Rainer )
• Genetic factors and gene-environment interactions in permanent coping with heavy smoking: retrospective life course analyses among 1,553 dependent heavy smokers (Applicant Brenner, Hermann )
• Genetic modulation of nicotine effects on emotional on reward processing (Applicant Smolka, Michael )
• Genetics of Nicotine Dependence: Clinical and Neurobiological Phenotypes in a Multicentered Case-Control-Study (Applicants Kiefer, Falk ;  Wagner, Ph.D., Michael ;  Wienker, Thomas F. ;  Winterer, Georg )
• Glutamatergic contributions to nicotine-induced cognitive enhancement (Applicant Hurlemann, Ph.D., René )
• Identification of functional nAChR variants and their role in nicotine addiction, schizophrenia and epilepsy (Applicants Bertrand, Daniel ;  Steinlein, Ortrud Kristina )
• Impact of the nicotinergic alpha7 receptor on cortical plasticity in smokers and nonsmokers (Applicant Nitsche, Michael A. )
• Nicotine cessation and withdrawal: alterations in neuroendocrine and sleep-polysomnographic parameters as predictors of relapse (Applicants Riemann, Dieter ;  Rodenbeck, Andrea )
• Nicotine effects on endophenotypes of schizophrenia (Applicant Wagner, Ph.D., Michael )
• Nicotine: Molecular and physiological effects on nicotine in central nervous system (Applicant Winterer, Georg )
• Protective mechanisms in nicotine-induced conditioned place preference and in vivo functional validation of candidate genes using rAAV (Applicant Lutz, Beat )
• Schizophrenia and Nicotine Addiction: Analysis of genetic mouse models (Applicant Zimmer, Andreas )
• Structure-function relationships of the VILlP-1 - a4ß2 nAChR interaction - implications for nicotine-induced functional up-regulation of the a4ß2 nicotinic acetylcholine receptor (Applicants Braunewell, Karl-Heinz ;  Manahan-Vaughan, Denise )
• The role of a4b2 nicotinic acetylcholine receptors in sustained attention: effects in smokers and non-smokers (Applicant Wüllner, Ullrich )

• Spokesperson: Professor Dr. Georg Winterer