Regional brain metabolic response to lorazepam in alcoholics during early and late alcohol detoxification

Alcohol Clin Exp Res. 1997 Oct;21(7):1278-84.


Changes in GABA function have been postulated to be involved in alcohol tolerance, withdrawal and addiction. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission), in alcoholics during early and late withdrawal. Brain metabolism was measured using PET and 2-deoxy-2[18F]fluoro-D-glucose after placebo (baseline) and after lorazepam (30 micrograms/kg intravenously) in 10 alcoholics and 16 controls. In the alcoholics evaluations were performed 2 to 3 weeks after detoxification and were repeated 6 to 8 weeks later. Controls were also evaluated twice at a 6 to 8 weeks interval. While during the initial evaluation metabolism was significantly lower for most brain regions in the alcoholics than in controls in the repeated evaluation the only significant differences were in cingulate and orbitofrontal cortex. Lorazepam-induced decrements in metabolism did not change with protracted alcohol withdrawal and the magnitude of these changes were similar in controls and alcoholics except for a trend towards a blunted response to lorazepam in orbitofrontal cortex in alcoholics during the second evaluation. Abnormalities in orbitofrontal cortex and cingulate gyrus in alcoholics are unlikely to be due to withdrawal since they persist 8 to 11 weeks after detoxification. The fact that there was only a trend of significance for an abnormal response to lorazepam in orbitofrontal cortex indicates that mechanisms other than GABA are involved in the brain metabolic abnormalities observed in alcoholic subjects.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alcohol Withdrawal Delirium / physiopathology
  • Alcohol Withdrawal Delirium / rehabilitation*
  • Alcoholism / physiopathology
  • Alcoholism / rehabilitation*
  • Blood Glucose / metabolism
  • Brain / drug effects*
  • Brain / physiopathology
  • Brain Mapping
  • Energy Metabolism / drug effects*
  • Energy Metabolism / physiology
  • Fluorodeoxyglucose F18 / metabolism
  • Frontal Lobe / drug effects
  • Frontal Lobe / physiopathology
  • GABA Modulators / pharmacology*
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / physiopathology
  • Humans
  • Lorazepam / pharmacology*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology
  • Reference Values
  • Tomography, Emission-Computed


  • Blood Glucose
  • GABA Modulators
  • Fluorodeoxyglucose F18
  • Lorazepam