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Am J Psychiatry 1993; 150:417-422
Copyright © 1993 by American Psychiatric Association
Decreased cerebral response to inhibitory neurotransmission in alcoholics
ND Volkow, GJ Wang, R Hitzemann, JS Fowler, AP Wolf, N Pappas, A Biegon and SL Dewey
Medical Department, Brookhaven National Laboratory, Upton, NY 11973.
OBJECTIVE: Changes in gamma-aminobutyric acid (GABA)-benzodiazepine
receptor function have been implicated in alcohol tolerance, withdrawal,
and dependence. The purpose of this study was to investigate whether
recently detoxified alcoholic subjects had abnormalities in brain
GABA-benzodiazepine receptor function. METHOD: The effect of 30
micrograms/kg of lorazepam on regional brain glucose metabolism was studied
in 12 normal subjects and 10 alcoholic subjects with the use of positron
emission tomography and [18F]fluorodeoxyglucose. RESULTS: Lorazepam
decreased whole brain glucose metabolism in both the normal subjects (13%
change) and the alcoholic subjects (10% change), and the response was
correlated with the concentration of lorazepam in plasma. Whereas the
normal and alcoholic subjects showed similar responses to lorazepam in
occipital and cerebellar metabolism, the alcoholic subjects showed
significantly less of a response than the comparison subjects in the
thalamus, basal ganglia, and orbitofrontal cortex. The rate of response in
the orbitofrontal cortex was significantly correlated with cerebellar
metabolism at baseline. CONCLUSIONS: The alcoholic subjects had a blunted
response to lorazepam that was specific to certain brain regions. The
association between cerebellar metabolism and response to lorazepam
suggests that the cerebellum may contribute to the decreased sensitivity to
lorazepam which was seen in the alcoholic subjects.
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