title: Regional brain metabolism during alcohol intoxication.
abstract: BACKGROUND
  Ethanol has a broad range of actions on many neurotransmitter systems. The depressant actions of ethanol in the brain are related in part to facilitation of gamma-aminobutyric acid (GABA) neurotransmission via its interaction with the benzodiazepine/GABA receptor complex. The purpose of this study was to evaluate the effects of ethanol on regional brain metabolism in 10 healthy right-handed men. The results were compared with those we previously published in a different group of 16 normal male subjects who received intravenous lorazepam, a benzodiazepine drug that also enhances GABA neurotransmission.
  
  
  METHODS
  The subjects were scanned with positron emission tomography and [F-18] fluorodeoxyglucose twice: 40 min after the end of placebo (diet soda) or ethanol (0.75 g/kg) oral administration. Image data sets were analyzed by using both the region of interest and the statistical parametric mapping (SPM) approach. SPM was used to generate a difference image between baseline and ethanol, which we compared to the difference image between baseline and lorazepam (30 microg/kg).
  
  
  RESULTS
  Ethanol significantly increased self-reports of "high" (p < or = 0.0001), dizziness (p < or = 0.004), and intoxication (p < or = 0.0001). Ethanol significantly decreased whole brain (-25 +/- 6%, p < or = 0.0001) and regional metabolism. Normalization of the regional measures by whole brain metabolism (relative measures) showed that ethanol decreased relative metabolic activity in occipital cortex (-4.9 +/- 4.1%, p < or = 0.006), whereas it increased relative metabolic act in left temporal cortex (+3.5 +/- 2.9%, p < or = 0.006) and left basal ganglia (+9 +/- 6.3%, p < or = 0.0009). SPM analyses revealed the same pattern of responses as the relative measures, showing decreases in occipital cortex and increases in left temporal cortex. Comparison of the relative measures and the SPM analyses obtained with lorazepam data revealed a similar pattern of effects, with relative decreases in occipital cortex (-7.8 +/- 4.8%) and relative increases in left temporal cortex (+3.8 +/- 5.7%). Lorazepam, but not ethanol, also decreased thalamic metabolism (-11.2 +/- 7.2%).
  
  
  CONCLUSIONS
  These results support similar though not identical mechanisms for the effects of alcohol and benzodiazepines on brain glucose metabolism. The fact that lorazepam, but not alcohol, reduced thalamic metabolism, an effect associated with sleepiness, could explain the higher sedative effects of lorazepam than of alcohol.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. gjwang@bnl.gov
authors.forename: G J
authors.initials: GJ
authors.lastname: Wang
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.forename: D
authors.initials: D
authors.lastname: Franceschi
authors.forename: J S
authors.initials: JS
authors.lastname: Fowler
authors.forename: P K
authors.initials: PK
authors.lastname: Thanos
authors.forename: N
authors.initials: N
authors.lastname: Scherbaum
authors.forename: N
authors.initials: N
authors.lastname: Pappas
authors.forename: C T
authors.initials: CT
authors.lastname: Wong
authors.forename: R J
authors.initials: RJ
authors.lastname: Hitzemann
authors.forename: C A
authors.initials: CA
authors.lastname: Felder
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000435:Alcoholic Intoxication / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D006801:Humans; D008140:Lorazepam / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D014055:Tomography, Emission-Computed
chemical_list: D002492:Central Nervous System Depressants; D018757:GABA Modulators; D010919:Placebos; D000431:Ethanol; D008140:Lorazepam