Sex-Dependent Behavioral Effects of the Neurosteroid Allopregnanolone (3α,5α-THP) in Neonatal and Adult Rats after Postnatal Stress

Abstract

The neuroactive steroid allopregnanolone (3a-hydroxy-5a-pregnan-20-one, 3α,5α-THP) has been shown to be involved in the central nervous system's response to stress. This experiment investigated whether response to the neuroactive steroid allopregnanolone, a positive modulator of the GABA A receptor, would be altered in neonatal or adult rats previously exposed to a chronic stressor–daily maternal separation during the first week of life. Subjects were then tested either as neonates or adults. In neonates, allopregnanolone decreased the number of ultrasonic vocalizations after brief maternal separation. Previously separated subjects vocalized less and were less active than controls, but were not more sensitive to allopregnanolone on either measure. In adulthood, subjects with a prior history of maternal separation had a greater grooming response to a novel environment after a 10-min cold water swim test than nonseparated subjects. Allopregnanolone reduced grooming, but, again, there was no difference due to stress history. A significant effect of gender was noted in the adult subjects—females were largely responsible for the effects reported. These results suggest that early maternal separation stress can produce an habituation response in neonates and a long-term sensitization response to later novel stress in adults. However, because the behavioral effects of allopregnanolone were not differentially influenced by this early stress history, the neuroactive steroid/GABA A receptor complex may not be the major mediator of these early stress sequela. Results indicating that females were more responsive to allopregnanolone than males are discussed in light of previous findings.