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 alp haxalone 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 a nd alprazolam reduced rearing activity in a dose-dependent manner, at doses that did not suppress climbing. The rearing-suppression effect o f alprazolam, but not of alphaxalone, was blocked by the benzodiazepin e antagonist flumazenil. No such dissociation between the effect on re aring and climbing was obtained with muscimol, and both activities wer e suppressed, in a flumazenil-insensitive pattern, at high doses. Cort icosterone and progesterone did not affect the behavior of the mice. T he lack of sensitivity of both phenobarbital and alphaxalone to flumaz enil indicates that neither agents act via the benzodiazepine recognit ion site at the GABA(A) receptor complex. (C) 1997 Elsevier Science B. V.