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Schad, Daniel J.; Garbusow, Maria; Friedel, Eva; Sommer, Christian; Sebold, Miriam; Haegele, Claudia; Bernhardt, Nadine; Nebe, Stephan; Kuitunen-Paul, Soeren; Liu, Shuyan; Eichmann, Uta; Beck, Anne; Wittchen, Hans-Ulrich; Walter, Henrik; Sterzer, Philipp; Zimmermann, Ulrich S.; Smolka, Michael N.; Schlagenhauf, Florian; Huys, Quentin J. M.; Heinz, Andreas and Rapp, Michael A. (2019): Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk. In: European Archives of Psychiatry and Clinical Neuroscience, Vol. 269, No. 3: pp. 295-308

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The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.

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