Sex-specific modulation of anxiety and locomotion after neonatal exposure to pregnenolone sulfate

Neurosteroids may influence adult behavior and endocrine function since early in development. To test this hypothesis, Sprague-Dawley pups from both sexes were injected with pregnenolone sulfate (PREG-S) from postnatal (PN) day 1 to 14. Pubertal onset in females was determined by monitoring the day of vaginal opening. After vaginal opening, the pattern of estrous cycle was monitored for three consecutive cycles. During adulthood, anxiety and locomotor activity were assessed with an automated elevated plus maze (EPM) and automated activity monitors, respectively. After behavioral assessment, body weight, gonadal weight, and plasma levels of sex hormones were measured. Neonatal exposure to PREG-S produced anxiolytic effects in females but not males. The opposite effect was seen in males, suppression of locomotor behaviors without changes in anxiety. The day of vaginal opening, gonadal weight, and plasma levels of hormones in adult animals were not altered by neonatal treatment. We suggest that PREG-S exposure during neonatal development can have an impact in anxiety and locomotor behaviors during adulthood in a sex-specific manner.