Die Rolle von Bassoon in dopaminergen Neuronen bei den konditionierten Verstärkereffekten von Alkohol am Mausmodell

Objectives: Alcohol dependence is a chronic disease that is prevalent worldwide. It develops through individual genetic predisposition, exposition, and the influence of environmental fac-tors. The treatment is difficult, especially due to frequent relapses. Bassoon, a protein found in presynapses, could offer a new approach in the treatment of alcohol dependence. Together with a few other proteins, it regulates the release cycle of neurotransmitters and is thus an important part of the signal transmission between neurons of various kinds. Design and Methods: In order to investigate the role of Bassoon in the brain's reward system regarding the development of alcohol dependence in animals, the protein was selectively knocked out in dopaminergic neurons in mice. The animals were then conditioned to specific environments by means of conditioned place preference under the influence of alcohol. All collected data were analysed in regard to sex and genotype for the underlying learning mecha-nisms of the conditioning. Observations and Results: It was shown that a conditioned place preference could be estab-lished in all animals. There were no differences between the sexes and genotypes. However, a difference was found when examining the influence of proximal stimuli as a sub-parameter of the conditioning. In the Bassoon mutant males, in comparison to all other groups, proximal stimuli could not be shown to be the decisive learning process for the establishment of the place preference. A clear reduction in the incentive value of proximal stimuli was shown, and thus a not unessential function of Bassoon in short-term memory, which processes the stimuli during the conditioning. Conclusions: A significant role of Bassoon in the conditioned reinforcing effects of alcohol cannot be assumed in the context of this work. However, due to the limited scope of the exper-iment, more intensive investigations with extended parameters are recommended. The obser-vation that Bassoon-mutated males show a shift in learning mechanisms could also serve as an approach for the development of a potential pharmacological relapse prophylaxis in alcohol dependence and thus as a basis for further research projects.