This study examined the effect of the neuroactive steroid 3 alpha, 5 a
lpha-tetrahydrodeoxycorticosterone (alpha-THDOC) as compared to the be
nzodiazepines diazepam and midazolam and the barbiturate phenobarbital
on the number of rearing events and the number of steps ascended in t
he mouse staircase test. The benzodiazepines, phenobarbital and alpha-
THDOC all reduced rearing activity at doses that did not affect climbi
ng. The rearing-suppression effect of the benzodiazepines and alpha-TH
DOC, but not of phenobarbital, was blocked by the benzodiazepine antag
onist flumazenil. It appears that, although such neuroactive steroids,
like barbiturates, bind to distinct sites within the chloride ion cha
nnel of the gamma-aminobutyric acid type A (GABA(A)) receptor complex,
alpha-THDOC behavioral activity is modulated by the benzodiazepine re
cognition site.