The Role of Dopaminergic and Glutamatergic Neurotransmission for Dysfunctional Learning in Alcohol Use Disorders
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcohol Drinking
Study type: Observational

Summary: 
      The aim of this project is to assess reward- based learning behavior and its association with
      alterations in dopaminergic and glutamatergic transmission in detoxified alcohol-dependent
      patients and matched controls.

      The investigators will explore how these alterations interact with clinical and psychosocial
      factors which can modify the relapse risk and learning deficits.

      Patients will be detoxified in an inpatient setting. Clinical assessments, behavioral
      paradigms of learning and brain imaging will be carried out within at least 4 half- lives
      after any psychotropic medication.

      The investigators will implement and apply functional imaging paradigms assessing
      Pavlovian-to-instrumental transfer and reversal learning tasks and associate model parameters
      of learning with alcohol craving, intake and prospective relapse risk.

      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).
    

Detailed description: 
      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.
    

Intervention name(s): Alcohol detoxification
Intervention type(s): Other
Intervention description(s): Detoxified alcohol- dependent patients in an inpatient setting
Other intervention name(s): Alcohol- dependent patients
Intervention MeSH terms: Ethanol
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Detoxified alcohol- dependent patients and age- and gender matched healthy controls living
        in Germany
      
Biospecimen description: 
      Bloodsample are taken for genetic analysis
    
Keywords: Reward- based learning; Pavlovian-to-instrumental transfer; Relapse Risk; Positron emission tomography (PET); Magnetic resonance spectroscopy (MRS); Dopamine receptor availability; Glutamate