Acute administration of a neurosteroid 5beta-pregnan-3alpha-ol-20-one
induced a greater impairment in motor performance of the selectively
bred alcohol-sensitive (ANT) than alcohol-insensitive (AT) rats. This
difference was not associated with the sensitivity of
gamma-aminobutyrate type A (GABA(A)) receptors, as
5alpha-pregnan-3alpha-ol-20-one (allopregnanolone) decreased the
autoradiographic signals of t-butylbicyclophosphoro[³⁵S]thionate binding
to GABA_A receptor-associated ionophores more in the brain sections of
AT than ANT rats. Nor was the difference associated with baseline
levels of neuroactive progesterone metabolites, as
5alpha-pregnan-3,20-dione (5alpha-DHP) and
5alpha-pregnan-3alpha-ol-20-one were lower in the ANT rats. After
ethanol (2 g/kg, i.p.) administration and the subsequent motor
performance test, the increased brain concentrations of these
metabolites were still lower in the ANT than AT rats, although
especially in the cerebellum the relative increases were greater in the
ANT than AT rats. The present data suggest that the mechanisms mediating
neurosteroid-induced motor impairment are susceptible to genetic
variation in rat lines selected for differences in ethanol intoxication.