Effect of the pregnane-related GABA-active steroid alphaxalone on mice performance in the staircase test.

We evaluated the modulatory effect of the GABA-active neurosteroid alphaxalone on the staircase test behavior of mice. Results were compared with the benzodiazepine alprazolam, the GABA(A) agonist muscimol and the peripheral steroids corticosterone and progesterone. Alphaxalone and alprazolam reduced rearing activity in a dose-dependent manner, at doses that did not suppress climbing. The rearing-suppression effect of alprazolam, but not of alphaxalone, was blocked by the benzodiazepine antagonist flumazenil. No such dissociation between the effect on rearing and climbing was obtained with muscimol, and both activities were suppressed, in a flumazenil-insensitive pattern, at high doses. Corticosterone and progesterone did not affect the behavior of the mice. The lack of sensitivity of both phenobarbital and alphaxalone to flumazenil indicates that neither agents act via the benzodiazepine recognition site at the GABA(A) receptor complex.