Involvement of Fibroblast Growth Factor-2 in alcohol use disorder

• Applicant: Professorin Dr. Claudia Grothe
• Subject Area: Biological Psychiatry ; Cognitive, Systems and Behavioural Neurobiology ; Molecular and Cellular Neurology and Neuropathology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 430949881

The working hypothesis of the proposal is that excessive alcohol exposure induces fibroblast growth factor 2 (FGF2)-dependent neuroadaptations in the nigrostriatal system, leading to abnormal function of the dopaminergic system, and to the development of a compulsive, out-of-control drinking and alcohol addiction phenotypes. The general objective of the proposed project is to elucidate the mechanisms, by which FGF2 interacts with alcohol-drinking behaviors, i.e. alcohol regulates FGF2 expression, and FGF2 regulates alcohol-drinking behaviors. We will gain better understanding on a) which of the different FGF2 isoforms and b) how they affect the midbrain-striatum dopaminergic pathways that control behaviors related to addiction, as well as the effects of alcohol exposure on this system. In particular, we will treat four objectives to characterize the interaction of the different players in the addiction-related scenario with regard to biochemical, molecular, morphological, and behavioral parameters, i.e. the FGF2 system, the dopaminergic system, and other FGF2-related alcohol consumption genes in the nigrostriatal system. First, we aim to determine the isoforms, cellular source and localization of FGF2 and its target cells during alcohol consumption. Second, we plan to analyze the FGF2-related gene expression in the midbrain-striatal system driven by alcohol consumption. Third, long-lasting morphological changes in dopaminergic neurons related to the FGF2 increase will be elucidated. Finally, we will test whether suppression of the FGF2 system prevents these neuroadaptations and reduces alcohol consumption and relapse, as a potential pharmacotherapeutic strategy to treat alcohol use disorder.

• DFG Programme: Research Grants
• International Connection: Israel
• International Co-Applicant: Professor Segev Barak, Ph.D.