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Schizophrenia and Nicotine Addiction: Analysis of genetic mouse models
Antragsteller
Professor Dr. Andreas Zimmer
Fachliche Zuordnung
Biologische Psychiatrie
Förderung
Förderung von 2009 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 146395062
This project addresses the molecular mechanisms that contribute to the high comorbidity of schizophrenia and nicotine addiction, by investigating the effect of nicotine in animal models with a deletion or transgenic over-expression of schizophrenia risk genes (DISC1, G72/G30, NRG3). We hypothesize that schizophrenic patients consume nicotine as a form of self-medication. Thus, acute and chronic nicotine administration might have beneficial effects on the behavioural deficits in paradigms for schizophrenia-like symptoms that have been observed in the genetic mouse models. Our alternative, not mutually exclusive, hypothesis is that the rewarding and/or addictive properties of nicotine are enhanced in genetic models of schizophrenia. This hypothesis will be tested by assessing the rewarding properties of nicotine in a place preference and operant self-administration paradigm. Further we will assess somatic signs of nicotine withdrawal after chronic administration. We will start to evaluate the molecular mechanisms that contribute to the anticipated differential effects of nicotine in these mouse models, by assessing nicotine receptor levels and downstream signalling pathways. These molecular studies will be guided by our (still unpublished) discovery of nicotine-induced transcriptional changes in specific brain regions, in the context of a NIH-funded project.
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Schwerpunktprogramme