Blockade of Cue-induced Brain Activation of Abstinent Alcoholics by a Single Administration of Amisulpride as Measured With fMRI Derik Hermann, Michael N. Smolka, Jana Wrase, Sabine Klein, Jo ¨ rg Nikitopoulos, Alexander Georgi, Dieter F. Braus, Herta Flor, Karl Mann, and Andreas Heinz Background: Once alcohol dependence is established, alcohol-associated cues may induce dopa- mine release in the reward system, which is accompanied by alcohol craving and may lead to relapse. In cocaine addicts, dopamine release in the thalamus was positively correlated with cocaine craving. We tested the effects of the atypical dopamine D 2/3 blocker amisulpride on cue-induced brain acti- vation in a functional magnetic resonance imaging (fMRI) paradigm. Methods: Alcohol-associated and neutral pictures were presented in a block design to 10 male abstinent alcoholics (1–3 weeks after detoxification) and 10 healthy men during fMRI. The fMRI scans were acquired before and 2 hours after the oral application of 400 mg amisulpride. Before and after each scan, alcohol craving was measured with visual analogue scales. Results: Before the application of amisulpride, alcohol versus control cues elicited a higher blood oxygen level–dependent (BOLD) signal in the left frontal and orbitofrontal lobe, left cingulate gyrus, bilateral parietal lobe, and bilateral hippocampus in alcoholics compared with healthy controls. After amisulpride, alcoholics showed a reduced activation in the right thalamus compared with the first scan. Alcoholics no longer showed significant differences in their cue-elicited BOLD response after amisulpride medication compared with medication-free controls. Self-reported craving was not affected by amisulpride medication. Conclusions: Amisulpride medication was associated with reduced cue-induced activation of the thalamus, a brain region closely connected with frontostriatal circuits that regulate behavior and may influence relapse risk. Key Words: Alcoholism, Amisulpride, fMRI. O N THE BASIS OF ANIMAL studies it was postu- lated that stimulus-induced release of dopamine may lead to heightened incentive salience of alcohol-associated cues in alcoholics (Robinson and Berridge, 1993). A sen- sitization of the dopamine reward system may be accompanied by alcohol craving (Robinson and Berridge, 1993). In agreement with this hypothesis, increased dopamine turnover was found in alcoholics when the dopamine metabolite homovanillic acid was determined in the cerebrospinal fluid of alcoholics with a high relapse risk (George et al., 1992, 1999). Postsynaptic striatal dopamine D 2 receptors were down-regulated in positron emission tomography (PET) and neuroendocrinologic studies of alcoholics (Heinz et al., 1996, 2004; Volkow et al., 1996). In the ventral striatum/nucleus accumbens, dopamine D 2 receptor availability was negatively correlated with alcohol craving and activation of the anterior cingulate gyrus by visual alcohol versus control cues (Heinz et al., 2004). When visual alcohol-associated cues were presented to recently abstinent alcoholics and control subjects, alcohol- ics showed an activation of the ventral striatum/nucleus accumbens, frontal cortices (the medial, orbital, and dorsolateral frontal cortex), the anterior cingulate gyrus, hippocampus/parahippocampal gyrus, and anterior thala- mus (Braus et al., 2001; George et al., 2001; Myrick et al., 2004; Tapert et al., 2003; Wrase et al., 2002). The brain activations that were induced in the striatum and anterior cingulate in response to visual alcohol-related stimuli were associated with increased subsequent relapse risk (Grusser et al., 2004). Several substances that influence dopaminergic neuro- transmission were tested to prevent alcohol relapse. However, both the use of traditional neuroleptics From the Central Institute of Mental Health, Mannheim, Germany (DH, MNS, JW, SK, JN, AG, DFB, HF, KM, AH); the Department of Psychi- atry of the Charite ´, Humboldt University, Berlin, Germany (JW, AH); and the NeuroImage Nord, Department of Psychiatry, University Med- ical Center, Hamburg-Eppendorf, Germany (DFB). Received for publication December 5, 2005; accepted April 12, 2006. This study was supported by the Deutsche Forschungsgemeinschaft (grant He 2597/7-2 and SM 80/1-1) and the German Ministry of Educa- tion and Research (Baden-Wu ¨rttemberg Consortium for Addiction Research No. 01 EB 0110/0410) and Sanofi Synthelabo. The first (DH) and second authors (MNS) contributed equally to this study. Reprint requests: Andreas Heinz, MD, Department of Psychiatry, Charite´—University Medicine Berlin, Campus Charite´ Mitte, Schu- mannstr. 20/21, 10117 Berlin, Germany; Fax: 149-30-450517921; E-mail: Andreas.Heinz@charite.de Copyright r 2006 by the Research Society on Alcoholism. DOI: 10.1111/j.1530-0277.2006.00174.x Alcohol Clin Exp Res, Vol 30, No 8, 2006: pp 1349–1354 1349 ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 30, No. 8 August 2006