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Altered benzodiazepine receptor sensitivity in alcoholism: a study with fMRI and acute lorazepam challenge.

Schlösser RG, Gesierich T, Wagner G, Bolz M, Gründer G, Dielentheis TF, Scherb C, Stoeter P

Department of Psychiatry, University of Jena, Philosophenweg 3, 07740 Jena, Germany. Ralf.Schloesser@uni-jena.de

Previous studies suggested altered sensitivity of the GABA/benzodiazepine receptor system in alcoholic patients. Expanding on these findings, the present functional magnetic resonance imaging (fMRI) study aimed to assess whether a differential modulation of cognitive brain activation by an acute GABAergic drug challenge could be detected in patients with alcoholism. Eight detoxified male patients meeting DSM-IV criteria for alcohol dependence and nine healthy male control subjects were studied with fMRI while performing a 2-back working memory task. The fMRI scans were performed 1 h after intravenous administration of saline and again 1 h after 0.03 mg/kg lorazepam I.V. After saline, a task x group interaction effect with higher task activation in alcoholic patients in the left cerebellum and the right prefrontal cortex emerged. Additionally, a differential task x drug x group interaction was identified in the right cerebellum with more pronounced reduction in cognitive activation after lorazepam in the patient group. A significant correlation between lorazepam sensitivity and duration of alcohol dependence was detected. The present findings are in line with previous studies suggesting disrupted prefrontal-cerebellar activation with potential compensatory hyperactivation of the compromised brain networks in alcoholism. Moreover, the results suggest enhanced responsivity to an acute GABAergic challenge in the right cerebellum with disease-related disruption of cerebellar functional integrity.

Published 26 March 2007 in Psychiatry Res, 154(3): 241-51.
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