Use of a novel mouse genotype to model acute benzodiazepine withdrawal

Pamela Metten, Kari Buck, Catherine M. Merrill, Amanda J. Roberts, Chia Hua Yu, John Jr Crabbe

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)160-170
Number of pages11
JournalBehavior Genetics
Volume37
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

benzodiazepines
GABA-A Receptors
Benzodiazepines
Seizures
drug
genotype
Genotype
seizures
mice
receptors
Pharmaceutical Preparations
agonists
drugs
Flumazenil
antagonists
Diazepam
Hypnotics and Sedatives
rodent
ethanol
Rodentia

Keywords

  • Abecarnil
  • Alprazolam
  • Benzodiazepines
  • Clonazepam
  • Diazepam
  • Handling-induced convulsions
  • Lorazepam
  • Midazolam
  • Mouse
  • Selected lines
  • Substance abuse
  • Triazolam
  • Withdrawal
  • Zolpidem

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Behavioral Neuroscience
  • Psychology(all)

Cite this

Use of a novel mouse genotype to model acute benzodiazepine withdrawal. / Metten, Pamela; Buck, Kari; Merrill, Catherine M.; Roberts, Amanda J.; Yu, Chia Hua; Crabbe, John Jr.

In: Behavior Genetics, Vol. 37, No. 1, 01.2007, p. 160-170.

Research output: Contribution to journalArticle

Metten, Pamela ; Buck, Kari ; Merrill, Catherine M. ; Roberts, Amanda J. ; Yu, Chia Hua ; Crabbe, John Jr. / Use of a novel mouse genotype to model acute benzodiazepine withdrawal. In: Behavior Genetics. 2007 ; Vol. 37, No. 1. pp. 160-170.
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