Mouse strains differ in their sensitivity to alprazolam effect in the staircase test.
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.
Weizman
R
R
Tel Aviv Community Mental Health Center, Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv, Israel.
Paz
L
L
Backer
M M
MM
Amiri
Z
Z
Modai
I
I
Pick
C G
CG
D000525:Alprazolam / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D011597:Psychomotor Performance / Q000187:drug effects*; D013045:Species Specificity
D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D005442:Flumazenil; D000525:Alprazolam