Neurosteroids during development: implications for behavior and stress sensitivity

Exposure of developing female rats to estradiol during the perinatal period induces long-lasting dysregulation of gonadal axis and alters brain and peripheral concentrations of steroid hormones. A single administration of beta-estradiol 3-benzoate (EB) on the day of birth to female rats induces a marked a persistent decrease in the concentrations of allopregnanolone and progesterone in the cerebral cortex, hypothalamus and hippocampus of juvenile and adult rats. These alterations are associated with increased agonistic behaviors in the resident-intruder test and a drastic reduction in spontaneous and induced female sexual behaviors, while locomotor activity, anxiety- and mood-related behaviors, as well as seizures sensitivity are not affected. Neonatal administration of EB also changes the expression of specific subunits of the GABAA receptor and enhances the sensitivity of adult rats to the anxiolytic, sedative-hypnotic, amnesic, but not anticonvulsant, effects of diazepam. Finally, neonatal administration of EB increases sensitivity of adult rats to acute stress, as demonstrated by the greater enhancement in brain allopregnanolone levels and in extracellular concentrations of dopamine and norepinephrine in the prefrontal cortex of EB-treated rats compared to vehicle-treated rats following exposure to foot shock stress. These effects of estradiol suggest that it plays a major role in the regulation of brain allopregnanolone concentrations during development and in the expression of behavior and stress sensitivity in adult female rats.