Sexual differentiation modifies the allopregnanolone anxiolytic actions in rats

The administration of progesterone (0.0, 1.0 and 2.0 mg/rat, SC) and allopregnanolone (5α, 3α dihydroprogesterone) (0.0, 0.5 and 1.0 mg/rat, SC) to both, males and females, produced a similar reduction in burying behavior. Only allopregnanolone showed a gender-dependent effect on burying behavior latency. Allopregnanolone actions were established in five groups of animals according to their neonatal hormonal manipulation: intact males and females, neonatally-testosterone propionate-treated female rats (TP, 30 and 120 μg/rat, SC at day 5) and neonatally (4-12 h after delivery) castrated males. Males and females showed a reduction in anxiety after treatment with allopregnanolone. Both neonatally-androgenized-females and -castrated males were completely insensitive to allopregnanolone anxiolytic action tested in both burying behavior and plus-maze paradigm. The virilizing action of neonatally administered TP was demonstrated by dose-dependent delayed vaginal opening, a persistent estrus in their vaginal smears and the presence of polifollicular ovaries. Results are discussed on the bases of the differences and similarities between males, females, androgenized females and neonatally castrated males to anxiolytic steroids and the underlying possible processes.