PRENATAL MORPHINE EXPOSURE ALTERS OVARIAN-STEROID HORMONAL-REGULATIONOF SEIZURE SUSCEPTIBILITY

The present study examined the ovarian hormonal regulation of seizure susceptibility in prenatally morphine- and saline-exposed adult female rats in the flurothyl seizure model in vivo, and in low-magnesium-ind uced epileptiform activity in brain slices, in vitro. All females were ovariohysterectomized (OVX); some received either estrogen (E) or pro gesterone (P) replacement, while others were injected with E + P seque ntially. In prenatally saline-treated control females, there was an in crease in the flurothyl-induced clonic seizure threshold (anticonvulsa nt effect) in the presence of both hormones (E + P) compared to OVX co ntrols. In morphine-exposed females, there was an increase in the flur othyl-induced clonic seizure threshold after an E injection alone whil e there was a reduced tonic-clonic seizure threshold in the presence o f both hormones (E + P) compared to the hormone treatment-matched grou p of saline-exposed females, In control females, in low magnesium medi um in vitro, the development of two types of epileptiform activity (se izure-like events and status of short discharges) was not affected by the different hormonal conditions. However, prenatal morphine exposure suppressed the development of both types of epileptiform activity in the E-injected females compared to the E-injected, control females. Th e present data demonstrate that the anticonvulsant effects of P on sei zure susceptibility requires the presence of E, Furthermore, prenatal morphine exposure alters ovarian steroid hormone-regulated seizure sus ceptibility. (C) 1998 Elsevier Science B.V. All rights reserved.