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Garbusow, M1,2, Schad, DJ3, Sommer, C4, Sebold, M1,2, Nebe, S4, Zimmermann, US4, Smolka, MN4, Huys, QJM5, Schlagenhauf, F1,6, Rapp, MA3, Heinz A1

1 Department of Psychiatry and Psychotherapy, Charité – Universitaetsmedizin Berlin, Germany
2 Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
3 Social and Preventive Medicine, University of Potsdam, Potsdam, Germany
4 Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany
5 Department of Biomedical Engineering, University of Zürich, Zürich, Switzerland
6 Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

Appetitive Pavlovian stimuli enhance instrumental behavior, theoretically formalized as Pavlovian-to-Instrumental-Transfer (PIT) effect. This phenomenon plays a key role in alcohol use disorders (AUD), because it has been shown, that conditioned alcohol-related cues trigger maladaptive behavior and lead to craving and relapse. Indeed, it has long been proposed that in addiction drug-associated cues acquire motivational properties via Pavlovian conditioning and thus control and generate drug seeking behavior. Animal and human studies showed that PIT recruits the mesolimbic dopaminergic reward system including the nucleus accumbens (NAcc). PIT was extensively assessed in animals and humans, but not in detoxified patients suffering from addiction. The research group “Learning in alcohol dependence (LeAD)” investigated a PIT paradigm with alcohol- and money-related stimuli during fMRI in AUD patients. We therefore established a modified PIT task (adapted from Huys et al. (2011)) measuring the effects of experimentally trained conditioned cues as well as the favorite alcoholic drink on instrumental go/nogo approach behavior. We observed a stronger money-related PIT NAcc activation in relapsers. Moreover, we found that the alcohol-related PIT effect was associated with a stronger nucleus accumbens activation in the group of patients suffering from alcohol dependence. Crucially, this effect were present in low severe dependent patients and subsequent abstainers but absent in high severe dependent patients and subsequent relapsers. Results from neural money- and alcohol-related PIT effects point to potential neurobiological risk and resilience factors. Results will be discussed with respect to possible therapeutical implications.