Regional Brain Metabolic Response to Lorazepam in Subjects at Risk for Alcoholism

Nora D. Volkow, Gene‐Jack ‐J Wang, Henri Begleiter, Robert Hitzemann, Naomi Pappas, Gail Burr, Katherine Pascani, Christopher Wong, Joanna S. Fowler, Alfred P. Wolf

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

The mechanisms underlying the blunted response to alcohol administration observed in subjects at risk for alcoholism are poorly understood and may involve GABA‐benzodiazepine receptors. The purpose of this study was to investigate if subjects at risk for alcoholism had abnormalities in brain GABA‐benzodiazepine receptor function. This study measured the effects of 30 μg/kg (iv) of lorazepam, on regional brain glucose metabolism using positron emission tomography and 2‐deoxy‐2[18F]fluoro‐d‐glucose in subjects with a positive family history for alcoholism (FP) (n= 12) and compared their response with that of subjects with a negative family history for alcoholism (FN) (n= 21). At baseline, FP subjects showed lower cerebellar metabolism than FN. Lorazepam decreased whole‐brain glucose metabolism, and FP subjects showed a similar response to FN in cortical and subcortical regions, but FP showed a blunted response in cerebellum. Lorazepam‐induced changes in cerebellar metabolism correlated with its motor effects. The decreased cerebellar baseline metabolism in FP as well as the blunted cerebellar response to lorazepam challenge may reflect disrupted activity of benzodiazepine‐GABA receptors in cerebellum. These changes could account for the decreased sensitivity to the motor effects of alcohol and benzodiazepines in FP subjects.

Original languageEnglish (US)
Pages (from-to)510-516
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume19
Issue number2
DOIs
StatePublished - Apr 1995

Keywords

  • Alcoholism
  • Benzodiazepines
  • Brain Glucose Metabolism
  • Cerebellum
  • Positron Emission Tomography

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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    Volkow, N. D., Wang, GJ. J., Begleiter, H., Hitzemann, R., Pappas, N., Burr, G., Pascani, K., Wong, C., Fowler, J. S., & Wolf, A. P. (1995). Regional Brain Metabolic Response to Lorazepam in Subjects at Risk for Alcoholism. Alcoholism: Clinical and Experimental Research, 19(2), 510-516. https://doi.org/10.1111/j.1530-0277.1995.tb01539.x