Altered benzodiazepine receptor sensitivity in alcoholism: a study with fMRI and acute lorazepam challenge.
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.
Schlösser
Ralf G M
RG
Department of Psychiatry, University of Jena, Philosophenweg 3, 07740 Jena, Germany. Ralf.Schloesser@uni-jena.de
Gesierich
Thomas
T
Wagner
Gerd
G
Bolz
Matthias
M
Gründer
Gerhard
G
Dielentheis
Thomas F
TF
Scherb
Claudius
C
Stoeter
Peter
P
D000328:Adult; D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D002531:Cerebellum / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D002719:Chlormethiazole / Q000627:therapeutic use; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D004334:Drug Administration Schedule; D018757:GABA Modulators / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D011594:Psychometrics; D011963:Receptors, GABA-A / Q000378:metabolism*
D018757:GABA Modulators; D011963:Receptors, GABA-A; D002719:Chlormethiazole; D008140:Lorazepam