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Neuronal effects of stress and modulation of extinction learning in alcohol use disorder (NeuroModel)

Subject Area Biological Psychiatry
Term from 2012 to 2019
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 186318919
 
Alcohol use disorder (AUD) is a chronic condition characterized by compulsive drug use despite adverse consequences and a high relapse risk that remains even after long periods of abstinence. Evidence suggests that stress and exposure to alcohol-associated stimuli contribute to these high relapse rates, however the precise relationship and neuropsychological mechanisms remain insufficiently understood. During the second Funding Period Project 8 (formerly Junior Group) will conduct two studies: 1. During the first Funding Period we demonstrated that patients¿ instrumental choice behaviour is susceptible to the influence of alcohol-associated environmental cues (the so-called Pavlovian-toinstrumental transfer effect, PIT) and confirmed a bias towards habitual behavioural control at the expense of goal-directed behaviour. Both mechanisms are linked to compulsive drug use and relapse in AUD. In healthy controls, stress is reported to bias the balance between goal-directed and habitual behavioural control, and preclinical studies have described effects of stress on PIT. Based on these findings, the aim of the first study of Project 8 is to investigate the influence of acute social stress on habitual control and on PIT in patients with AUD. We hypothesize that stress will further diminish the influence of goal-directed behaviour and related prefrontal learning signals and increase the PIT effect and its associated striatal activation in AUD. Psychosocial stress will be induced using the standardized "Trier Social Stress Test" (TSST) and compared with a control condition using fMRI and a within subject repeated-measures design in AUD patients and matched controls. 2. Pavlovian appetitive conditioning contributes to the motivational power of alcohol-associated cues, therefore potential interventions that target these Pavlovian effects are of great clinical importance. Research on fear extinction is a prime example of successful translational research generating powerful intervention strategies. However, controlled human laboratory studies investigating appetitive conditioning, including effects of drug-associated cues are lacking. The second study of Project 8 will therefore investigate behavioural and neuronal effects of an extinction manipulation on the response to appetitive Pavlovian cues. The effect of a novel memory retrieval-extinction procedure to prevent the reinstatement of extinguished appetitive Pavlovian cues will be compared to a standard extinction procedure and tested in healthy controls.
DFG Programme Research Units
 
 

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