Dysfunctional interaction of dopamine and glutamate as a predictor for the development of alcohol use disorders (AUD)

• Applicant: Professor Dr. Felix Bermpohl, since 9/2014
• Subject Area: Biological Psychiatry
• Term: from 2012 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 186318919

Alcohol consumption despite negative consequences may rely on impaired flexibility in adapting the behavior to environmental changes, i.e. learning in response to reward contingencies. This learning deficit is of clinical relevance particularly during therapy and for the psychosocial outcome. The reduced availability of central dopamine D2-receptors in detoxified alcohol dependent patients observed in PET investigations and their hypothetical effects on reward-related learning are in line with evidence for learning deficits in hypodopaminergic states, particularly for avoidance learning in non-dependent samples. Growing evidence indicates that the learning-related striatal dopamine signals are modulated by higher executive functions involving, e.g., the prefrontal cortex. Here, broad glutamatergic outputs of the prefrontal cortex are crucial for subcortical learning mechanisms and match with recent models of interactive dopamine-glutamate dysfunctions and models of neurotrophic signaling in alcohol dependence. In this project, the impact of the dopamine x glutamate interaction on learning deficits and consecutive relapse probability is targeted with [18F]fallypride PET and the measurement of absolute concentrations of glutamate with magnetic resonance spectroscopy (MRS).

• DFG Programme: Research Units
• Subproject of: FOR 1617: Learning and Habitisation as Predictors of the Development and Maintenance of Alcoholism
• Participating Persons: Ralph Buchert, Ph.D.; Professor Dr. Andreas Heinz; Professor Dr. Rainer Hellweg
• Ehemaliger Antragsteller: Professor Dr. Jürgen Gallinat, until 9/2014