Effect of the neuroactive steroid alpha-THDOC on staircase test behavior in mice.

This study examined the effect of the neuroactive steroid 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone (alpha-THDOC) as compared to the benzodiazepines diazepam and midazolam and the barbiturate phenobarbital on the number of rearing events and the number of steps ascended in the mouse staircase test. The benzodiazepines, phenobarbital and alpha-THDOC all reduced rearing activity at doses that did not affect climbing. The rearing-suppression effect of the benzodiazepines and alpha-THDOC, but not of phenobarbital, was blocked by the benzodiazepine antagonist flumazenil. It appears that, although such neuroactive steroids, like barbiturates, bind to distinct sites within the chloride ion channel of the gamma-aminobutyric acid type A (GABAA) receptor complex, alpha-THDOC behavioral activity is modulated by the benzodiazepine recognition site.