Effects of Early Postnatal Allopregnanolone Administration on Elevated Plus Maze Anxiety Scores in Adult Male Wistar Rats

Abstract

Background/Aims: Recent findings suggest that neurosteroids are involved in brain development. The present study focused on the long-term effects of developmentally altered allopregnanolone (AlloP) levels on anxiety-like behavior in adulthood. Method: We administered AlloP (10 mg/kg) to rat pups once a day from the 5th to the 9th day after birth. A dose-response study on midazolam in the elevated plus maze test was carried out in adulthood (experiment 1) in order to screen GABAA-benzodiazepine function alterations. Given that the anxiety-like responses were not affected by AlloP, we doubled the initial AlloP dose (experiment 2). One group of pups was left undisturbed with their dams in order to control the effects of daily handling. Only males were behaviorally tested. Results: Neonatal AlloP administration (10 mg/kg) did not alter the behavioral response to midazolam in adulthood at the doses tested. Neonatal AlloP administration at the higher dose (20 mg/kg) induced an anxiolytic-like profile in adulthood (increased entries into and time spent in the open arms), without affecting motor activity. The behavioral effects of neonatal AlloP administration were both selective and independent of daily handling. Conclusion: Alterations in AlloP levels during maturation could partly explain the interindividual differences shown by adult subjects in response to environmental stress.