PRENATAL STRESS EFFECTS ARE PARTIALLY AMELIORATED BY PRENATAL ADMINISTRATION OF THE NEUROSTEROID ALLOPREGNANOLONE

This study examined the effects of exposure to prenatal stress on youn g and adult rats, and whether the concomitant administration of an anx iolytic neurosteroid, allopregnanolone (3-alpha-hydroxy-5 alpha-pregna n-20-one), could ameliorate some of the behavioral dysfunction associa ted with prenatal stress. Pregnant darns were assigned to one of five treatment groups on gestational day 14. These groups were exposed to e ither 1) restraint for 45 min three times daily; 2) a vehicle injectio n twice daily; 3) 5 mg/kg allopregnanolone twice daily; 4) restraint w ith allopregnanolone injections; or 5) nonhandled controls. Assays for plasma allopregnanolone concentrations indicated that exogenous allop regnanolone injections significantly raised circulating levels to a co mparable degree in gestational day 20 dams and their fetuses. At 7 day s of age, however, subjects prenatally exposed to allopregnanolone eit her alone or with restraint now had lower circulating levels compared to the other groups, suggesting some negative compensatory change. Beh avioral results suggested that the effects of prenatal stress on affec tive behaviors (ultrasonic vocalizations emitted after a brief materna l separation at 7 days of age, and plus-maze behavior at 70 days of ag e) could be reversed by coadministration of allopregnanolone. When loc omotor activity was assessed at 16 and 60 days of age, no comparable r eversal 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 teratogen ic effect or an indirect effect due to neurosteroid-induced behavioral changes in the pregnant dam. (C) 1998 Elsevier Science Inc.