Behavior Genetics

, Volume 37, Issue 1, pp 160–170

Use of a Novel Mouse Genotype to Model Acute Benzodiazepine Withdrawal

  • Pamela Metten
  • Kari J. Buck
  • Catherine M. Merrill
  • Amanda J. Roberts
  • Chia-Hua Yu
  • John C. Crabbe
Original Paper

DOI: 10.1007/s10519-006-9094-3

Cite this article as:
Metten, P., Buck, K.J., Merrill, C.M. et al. Behav Genet (2007) 37: 160. doi:10.1007/s10519-006-9094-3

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.

Keywords

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

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Pamela Metten
    • 1
    • 2
  • Kari J. Buck
    • 1
    • 3
  • Catherine M. Merrill
    • 1
    • 2
  • Amanda J. Roberts
    • 4
  • Chia-Hua Yu
    • 1
    • 2
  • John C. Crabbe
    • 1
    • 2
  1. 1.Department of Behavioral Neuroscience, Portland Alcohol Research CenterOregon Health & Science UniversityPortlandUSA
  2. 2.Department of Veterans Affairs Medical CenterR&D-12PortlandUSA
  3. 3.Department of Veterans Affairs Medical CenterR&D-40PortlandUSA
  4. 4.Molecular and Integrative Neurosciences DepartmentThe Scripps Research InstituteLa JollaUSA

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