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Use of a novel mouse genotype to model acute benzodiazepine withdrawal

Academic Article
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Overview

authors

  • Metten, P.
  • Buck, K. J.
  • Merrill, C. M.
  • Roberts, Amanda
  • Yu, C. H.
  • Crabbe, J. C.

publication date

  • January 2007

journal

  • Behavior Genetics  Journal

abstract

  • Withdrawal from benzodiazepines in physically dependent rodents often requires that the drug be dislodged from its receptor with a competitive antagonist. Withdrawal Seizure-Prone (WSP) mice were selectively bred for their susceptibility to handling-induced withdrawal convulsions following chronic treatment with ethanol. Reflecting pleiotropic genetic influences, they also experience more severe withdrawal from other sedative-hypnotics including the benzodiazepine, diazepam. We used this susceptible genotype to test whether other benzodiazepine receptor (BZR) agonists also produce physical dependence following acute administration, comparing studies of spontaneous withdrawal with those where convulsions were precipitated by a BZR antagonist (flumazenil). Separate groups of mice were tested following a single injection of one of eight BZR agonists. Several doses of each drug were tested for spontaneous withdrawal, and a single dose of each drug was tested for precipitated withdrawal. Withdrawal convulsions were seen after all of the drugs by at least one method, suggesting that BZR agonists as a class elicit acute physical dependence in this susceptible genotype.

subject areas

  • Animals
  • Anti-Anxiety Agents
  • Benzodiazepines
  • Disease Models, Animal
  • Female
  • GABA-A Receptor Antagonists
  • Genotype
  • Mice
  • Mice, Inbred Strains
  • Receptors, GABA-A
  • Seizures
  • Substance Withdrawal Syndrome
  • Time Factors
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Research

keywords

  • abecarnil
  • alprazolam
  • benzodiazepines
  • clonazepam
  • diazepam
  • handling-induced convulsions
  • lorazepam
  • midazolam
  • mouse
  • selected lines
  • substance abuse
  • triazolam
  • withdrawal
  • zolpidem
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Identity

International Standard Serial Number (ISSN)

  • 0001-8244

Digital Object Identifier (DOI)

  • 10.1007/s10519-006-9094-3

PubMed ID

  • 17226103
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Additional Document Info

start page

  • 160

end page

  • 170

volume

  • 37

issue

  • 1

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