Mouse strains differ in their sensitivity to alprazolam effect in the staircase test

Ronit Weizman, Lior Paz, Maria M. Backer, Zamir Amiri, Ilan Modai, Chaim G. Pick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The behavioral responses of five mouse strains (inbred: C57 and BALB/c; outbred: Swiss, ICR and HS/Ibg) to alprazolam was examined in the staircase test, an animal model sensitive to benzodiazepines (BZs). Alprazolam administration resulted in a dose-dependent suppression of rearing behavior, but to a different extent among the strains. By contrast, the number of stairs ascended was not suppressed by alprazolam at doses of 0.25 and 0.5 mg/kg, except in the C57 mice. The addition of flumazenil antagonized the alprazolam effect on rearing and climbing in all strains. There was a consistency within strains in sensitivity to alprazolam, with some strains being highly sensitive (C57 and HS) or less sensitive (Swiss, ICR and BALB/c) with regard to both rearing and climbing behaviors. Serum alprazolam levels did not differ significantly among the strains. This strain-dependent pattern of response to alprazolam seems to indicate a genetic component, rather than pharmacokinetic, in the behavior sensitivity to the BZ, with a spectrum of degree of responsivity among strains.

Original languageEnglish
Pages (from-to)58-65
Number of pages8
JournalBrain Research
Volume839
Issue number1
DOIs
StatePublished - 21 Aug 1999

Keywords

  • Alprazolam
  • Benzodiazepine/GABA receptor complex
  • Flumazenil
  • Mouse strain
  • Staircase test

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