Prenatal stress reduces the effectiveness of the neurosteroid 3 alpha,5 alpha-THP to block kainic-acid-induced seizures

The effects of prenatal stress on the ability of the 5 alpha-reduced proges terone metabolite and neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one (3 alp ha,5 alpha-THP) to pl el ent seizures was examined. On gestational Day 18, pregnant rats were exposed to 20 min of restraint stress (prenatal stress c ondition) or no such stress (control condition). The adult, gonadectomized offspring exposed to the prenatal stress or control condition were administ ered 0.0, 4.0, or 8.0 mg/kg 3 alpha,5 alpha-THP 1 hr prior to testing for k ainic-acid-induced (32 mg/kg SC) ictal activity. The rats exposed to prenat al stress tended to have more partial seizures and significantly more tonic clonic seizures that Mere of longer duration than the no prenatal stress r ats. Four mg/kg 3 alpha,5 alpha-THP was sufficient to significantly reduce seizure duration of no prenatal stress females, compared to the 0.0 mg/kg d osage of 3 alpha,5 alpha-THP. Seizure duration was reduced in no prenatal s tress females by a dose of 4 mg/kg 3 alpha,5 alpha-THP, whereas a dose of 8 mg/kg was required to obtain comparable seizure reduction in prenatally st ressed females and males in both groups. There was attrition following kain ic-acid testing; of the 18 animals in Each group originally, 9 prenatally s tressed males, 6 prenatally stressed females, 6 nonprenatally stressed male s and 5 nonprenatally stressed females were able to be tested in the water maze and perfused. One week after seizures, there were no differences in th e water maze performance of the remaining animals. There were fewer cresyl violet-stained neurons in the CA3 region of the hippocampus of prenatally s tressed rats compared to the nonprenatally stressed rats. Basal plasma cort icosterone was greater in prenatally stressed animals, bur this was due to increases in females rather than males. Plasma 3 alpha,5 alpha-THP was not significantly different in prenatally stressed males and females compared t o their no prenatal stress counterparts. These data suggest that the sensit ivity to, or responsiveness of, 3 alpha,5 alpha-THP to prevent seizures is decreased after prenatal stress, particularly in females. (C) 1999 John Wil ey & Sons, Inc.