Neonatal exposure to estradiol influences allopregnanolone concentrations and behavior in the adult female rat

During perinatal period gonadal steroids exert an important action in the regulation of sexual dimorphism of nervous system. This study aimed to evaluate the effect of a single administration of 10 ?g of ?-estradiol 3-benzoate (EB) to female rats on the day of birth on brain and plasma concentrations of the neuroactive steroid allopregnanolone (AP), general behaviors and sensitivity to diazepam (DZ). Neonatal EB administration induces a dramatic reduction in the cerebrocortical and plasma levels of AP in both juvenile and adult (21 and 60 days) female rats. Given that AP elicits anxiolytic, antidepressant, anticonvulsant and sedative effects, and facilitates social behavior, we assessed whether this treatment might alter emotional, cognitive and social behaviors. Neonatal EB treatment did not affect locomotor activity, anxiety- and mood-related behaviors, seizures sensitivity and spatial memory. In contrast, neonatal EB administration increased sensitivity to the anxiolytic, sedative, and amnesic effects of DZ in adult female rats. These results indicate that the persistent reduction in the cerebrocortical and peripheral AP levels, induced by neonatal treatment with EB, seems to be associated to changes in the behavioral sensitivity to the positive allosteric modulator of the GABAA receptor, DZ. These effects suggest that estradiol plays a major role in the pharmacological regulation of the GABAergic transmission in the central nervous system.