Prenatal stress effects are partially ameliorated by prenatal administration of the neurosteroid allopregnanolone

This study examined the effects of exposure to prenatal stress on young and adult rats, and whether the concomitant administration of an anxiolytic neurosteroid, allopregnanolone (3-alpha-hydroxy-5 alpha-pregnan-20-one), could ameliorate some of the behavioral dysfunction associated with prenatal stress. Pregnant darns were assigned to one of five treatment groups on gestational day 14. These groups were exposed to either 1) restraint for 45 min three times daily; 2) a vehicle injection twice daily; 3) 5 mg/kg allopregnanolone twice daily; 4) restraint with allopregnanolone injections; or 5) nonhandled controls. Assays for plasma allopregnanolone concentrations indicated that exogenous allopregnanolone injections significantly raised circulating levels to a comparable degree in gestational day 20 dams and their fetuses. At 7 days of age, however, subjects prenatally exposed to allopregnanolone either alone or with restraint now had lower circulating levels compared to the other groups, suggesting some negative compensatory change. Behavioral results suggested that the effects of prenatal stress on affective behaviors (ultrasonic vocalizations emitted after a brief maternal separation at 7 days of age, and plus-maze behavior at 70 days of age) could be reversed by coadministration of allopregnanolone. When locomotor activity was assessed at 16 and 60 days of age, no comparable reversal effect was observed. In fact, the allopregnanolone groups had results similar to those of the restraint alone group. Thus, for some neuronal systems, allopregnanolone may exert either a direct teratogenic effect or an indirect effect due to neurosteroid-induced behavioral changes in the pregnant dam. (C) 1998 Elsevier Science Inc.