Interactions between benzodiazepine antagonists, inverse agonists, and acute behavioral effects of ethanol in mice

Peter J. Syapin, Brenda L. Jones, Leigh S. Kobayashi, Deborah A. Finn, Ronald L. Alkana

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The behavioral manifestations of acute ethanol intoxication resemble those of benzodiazepines, barbiturates and general anesthetics. This has led to speculation that these drugs share common mechanisms or sites of actions within the brain. The discovery of a specific benzodiazepine receptor site, and the subsequent development of selective receptor antagonist and inverse agonist drugs, provides a framework to test the involvement of the benzodiazepine receptor complex in mediating ethanol's behavioral effects. The partial inverse agonist Ro15-4513, an analog of the benzodiazepine receptor antagonist Ro15-1788 (flumazenil), has been reported to block or reduce some of ethanol's acute effects in rodents by a benzodiazepine receptor-mediated action. There has been some controversy over whether the "antialcohol" effect of Ro15-4513 is a unique property of this compound or is shared by other benzodiazepine antagonists with inverse agonist activity. We have studied the effects of Ro15-4513 and other benzodiazepine receptor antagonists on acute ethanol intoxication in mice and have obtained evidence that 1. 1) Ro15-4513 differentially affects acute effects of ethanol, 2. 2) an "antialcohol" property is not a general feature of all benzodiazepine antagonists and inverse agonists, and 3. 3) "antialcohol" activity may not be unique to Ro15-4513.

Original languageEnglish (US)
Pages (from-to)705-709
Number of pages5
JournalBrain Research Bulletin
Volume24
Issue number5
DOIs
StatePublished - May 1990

Keywords

  • Acute ethanol
  • Alcohol antagonists
  • Alcohol hypnosis
  • Alcohol hypothermia
  • Alcohol stimulation
  • Benzodiazepine antagonists
  • FG7142
  • Flumazenil
  • Inverse agonists
  • Locomotor activity
  • Mice
  • Ro15-4513

ASJC Scopus subject areas

  • Neuroscience(all)

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