A National Research Priority Program of  
the

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Funding Period 2010 - 2013

P2

A multimodal genomic imaging study on the effects of nicotine and nicotine withdrawal on brain circuits using simultaneous EEG/EMG, fMRI and PET (WI 1316/7-2)

Succeeding project of "Attentional network, nicotine-dependence and alpha4beta2 nAch receptor genotype in healthy subjects and schizophrenic patients"


Georg Winterer, MD, PhD, (Principle Investigator)
Cologne Center for Genomics
University of Cologne
Weyertal 115b
50931 Cologne
+49-221-478-96847
Fax: +49-221-478-96866
georg.winterer(at)uni-koeln.de

 

Dr. Amalia Díaz-Lacava

Cologne Center for Genomics

University of Cologne

Weyertal 115b

50931 Cologne

a.díaz-lacava(at)uni-koeln.de

 

Nina Feyerabend

Cologne Center for Genomics

University of Cologne

Weyertal 115b

50931 Cologne

nina.feyerabend(at)uni-koeln.de

+49-221-478-96845

 

 

Together with:

 

Prof. Dr. Gerhardt Gründer (Principle Investigator)

RWTH University Aachen

Dept. of Psychiatry

Pauwelsstr. 30

52074 Aachen http://www.ukaachen.de/img/space.gif

+49-241-80 89821/ 88415 http://www.ukaachen.de/img/space.gif http://www.ukaachen.de/img/space.gif http://www.ukaachen.de/img/space.gif

Fax: +49-241-80 33 88415 http://www.ukaachen.de/img/space.gif

ggruender(at)ukaachen.de http://www.ukaachen.de/img/space.gif

 

Dr. med. Arian Mobascher

Psychiatrische Klinik und Poliklinik

Johannes Gutenberg Universität Mainz

Untere Zahlbachstr.

55131 Mainz

+49-6131-17-2140

Fax: +49-6131-17-6690

mobascher_a(at)psychiatrie.klinik.uni-mainz.de

 

Dr. Katja Spreckelmeyer
RWTH University Aachen
Dept. of Psychiatry
Pauwelsstr. 30

52074 Aachen
+49-241-8088550

Fax: +49-241-8089821

kspreckelmeyer(at)ukaachen.de

 

Dr. Ingo Vernaleken
RWTH University Aachen
Dept. of Psychiatry
Pauwelsstr. 30

52074 Aachen
+49-241-80-89654

Fax: +49-241-80 33 88415
ivernaleken(at)ukaachen.de

 

Project Partner:

 

Research Center Juelich (Helmholtz Institute)
Institute of Neuroscience and Medicine (INM-4)
Research Center Juelich
52425 Juelich
Prof. Dr. N.J. Shah (Principle Investigator)
+49-2461-61-6836
Fax: +49-2461-61-1919
n.j.shah(at)fz-juelich.de

 

Prof. Dr. Hans Herzog
PET-Physics
Institute of Neuroscience and Medicine (INM-4)
Research Center Juelich
52425 Juelich
+49-2461-61-5913
Fax: +49-2461-61-8310

h.herzog(at)fz-juelich.de

 

Dr. Irene Neuner

RWTH University Aachen

Dept. of Psychiatry

Pauwelsstr. 30

52074 Aachen

+49-241-80-89648

ineuner(at)ukaachen.de

 

Dr. Tracy Warbrick

Institute of Neuroscience and Medicine (INM-4)
Research Center Juelich
52425 Juelich

+49-2461-61-1918
Fax: +49-2461-61-1919

t.warbrick(at)fz-juelich.de

 

Nicotine modulates several brain circuits such as the neuronal networks involved in attention, working memory, sensorimotor gating and reward. This is achieved by activating nicotinic acetylcholine receptors (nAChR) on glutamatergic, GABAergic, cholinergic and monoaminergic (and in that regard especially dopaminergic) neurons. This way nicotine can improve cognitive functioning, information filtering, i.e. improve gating out of irrelevant stimuli and thus becomes habit-forming and ultimately causes nicotine addiction. However, the individual response of the respective neuronal networks to nicotine, the behavioural correlate of nicotinic stimulation and the risk to become an addicted smoker after exposure to nicotine are highly variable form subject to subject and are under genetic control. Furthermore, the relative contribution of individual downstream transmitter systems (e.g. the dopaminergic systems) to the central effects of nicotine remains to be elucidated.

In the present study we intend to merge data from the largely complementary methods: functional magnetic resonance imaging (fMRI), electroencephalography (EEG), startle reflex measurement and positron emission tomography (PET) using the highly selective dopamine D2/3 receptor ligand [18F] fallypride to study genotype-dependent effects of nicotine on the central nervous system. Taking advantage of this newly established imaging platform at the Helmholtz Research Center Juelich, which is worldwide unique, all data will be obtained simultaneously during multimodal psychophysiological experiments. Smokers (N=50) and never-smoking controls (N=50) will be investigated twice (one week apart) applying a placebo-controlled cross-over design (nicotine patches). All subjects will be scanned both under placebo and nicotine condition. Subjects will spend a nicotine-free night prior to each experiment on the research unit in Juelich. As opposed to the study that has been conducted during the first funding period, probands will not be selected blind for genotype but instead selected by genotype. Accordingly, probands with genetic variations will be chosen in advance and compared to subjects without this genotype. For this purpose, all subjects will be recruited from the “Nicotine Multicenter Study” which has been conducted within the framework of the Nicotine Priority Program 1226. In the “Multicenter Study”, a large population-representative sample of N =2.500 smokers and never-smokers has been collected and extensively (endo-)phenotyped throughout Germany. DNA is available for all subjects. The gene(s) of interest are CHRNA3, CHRNA4 and CHRNA5. We hypothesize positive relationships between nicotine-induced dopamine release, EEG- and fMRI-brain activity measures and behavioural responses related to cognition and the rewarding effects of nicotine. We furthermore hypothesize an impact of smoking status and of genetic variations in the selected nAChR gene on the “read-out” measures as obtained from simultaneous PET-, EEG- and fMRI under placebo-conditions as well as under nicotine challenge.