Behavior Genetics

, Volume 28, Issue 2, pp 125–136

Genotypic Differences Between C57BL/6 and A Inbred Mice in Anxiolytic and Sedative Actions of Diazepam

  • Kennon M. Garrett
  • Iwona Niekrasz
  • Dewan Haque
  • K. Michael Parker
  • Thomas W. Seale
Article
  • 133 Downloads

Abstract

The role of genotype in susceptibility to the behavioral actions of benzodiazepines is not well characterized. To develop a model for such studies, we have characterized the anxiolytic and sedative activities of diazepam in C57BL/6J and A/J inbred mice. C57BL/6J mice were more responsive than A/J mice to diazepam-induced anxiolytic-like activity in the mirrored chamber aversion assay and the elevated plus-maze assay. Basal activity of the two strains did not differ in either assay. In contrast, the two strains were equally responsive to the anxiolytic effects of the 5-HT1Areceptor partial agonist, buspirone. C57BL/6J mice were also more susceptible to the sedative effects of diazepam than were A/J mice. Flumazenil blocked the effects of diazepam in these behavioral assays. Measurement of diazepam and nordiazepam in blood and brain suggested that the response differences are of a pharmacodynamic rather than a pharmacokinetic nature. Taken together, these findings indicate that C57BL/6J and A/J mice provide a valuable tool for behavioral genetic studies of the mechanisms underlying the pharmacological actions of benzodiazepines.

Benzodiazepines GABAAreceptor inbred mice pharmacogenetics anxiety sedation 

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Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Kennon M. Garrett
    • 1
  • Iwona Niekrasz
    • 2
  • Dewan Haque
    • 1
  • K. Michael Parker
    • 3
  • Thomas W. Seale
    • 4
  1. 1.Department of PhysiologyUSA
  2. 2.Department of PediatricsUSA
  3. 3.Department of PathologyUniversity of Oklahoma Health Sciences CenterOklahoma City
  4. 4.Department of PediatricsUniversity of Oklahoma Health Sciences CenterOklahoma City

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