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Prenatal stress reduces the effectiveness of the neurosteroid 3α,5α‐THP to block kainic‐acid‐induced seizures
Author(s) -
Frye Cheryl A.,
Bayon Laura E.
Publication year - 1999
Publication title -
developmental psychobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 93
eISSN - 1098-2302
pISSN - 0012-1630
DOI - 10.1002/(sici)1098-2302(199904)34:3<227::aid-dev7>3.0.co;2-h
Subject(s) - prenatal stress , kainic acid , endocrinology , medicine , allopregnanolone , offspring , pregnancy , gestation , status epilepticus , neuroactive steroid , epilepsy , biology , gabaa receptor , receptor , psychiatry , glutamate receptor , genetics
The effects of prenatal stress on the ability of the 5α‐reduced progesterone metabolite and neurosteroid 5α‐pregnan‐3α‐ol‐20‐one (3α,5α‐THP) to prevent seizures was examined. On gestational Day 18, pregnant rats were exposed to 20 min of restraint stress (prenatal stress condition) or no such stress (control condition). The adult, gonadectomized offspring exposed to the prenatal stress or control condition were administered 0.0, 4.0, or 8.0 mg/kg 3α,5α‐THP 1 hr prior to testing for kainic‐acid‐induced (32 mg/kg SC) ictal activity. The rats exposed to prenatal stress tended to have more partial seizures and significantly more tonic clonic seizures that were of longer duration than the no prenatal stress rats. Four mg/kg 3α,5α‐THP was sufficient to significantly reduce seizure duration of no prenatal stress females, compared to the 0.0 mg/kg dosage of 3α,5α‐THP. Seizure duration was reduced in no prenatal stress females by a dose of 4 mg/kg 3α,5α‐THP, whereas a dose of 8 mg/kg was required to obtain comparable seizure reduction in prenatally stressed females and males in both groups. There was attrition following kainic‐acid testing; of the 18 animals in each group originally, 9 prenatally stressed males, 6 prenatally stressed females, 6 nonprenatally stressed males 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 the water maze performance of the remaining animals. There were fewer cresyl violet‐stained neurons in the CA3 region of the hippocampus of prenatally stressed rats compared to the nonprenatally stressed rats. Basal plasma corticosterone was greater in prenatally stressed animals, but this was due to increases in females rather than males. Plasma 3α,5α‐THP was not significantly different in prenatally stressed males and females compared to their no prenatal stress counterparts. These data suggest that the sensitivity to, or responsiveness of, 3α,5α‐THP to prevent seizures is decreased after prenatal stress, particularly in females. © 1999 John Wiley & Sons, Inc. Dev Psychobiol 34: 227–234, 1999