Prenatal morphine exposure alters ovarian steroid hormonal regulation of 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-induced epileptiform activity in brain slices, in vitro. All females were ovariohysterectomized (OVX); some received either estrogen (E) or progesterone (P) replacement, while others were injected with E + P sequentially. In prenatally saline-treated control females, there was an increase in the flurothyl-induced clonic seizure threshold (anticonvulsant effect) in the presence of both hormones (E + P) compared to OVX controls. In morphine-exposed females, there was an increase in the flurothyl-induced clonic seizure threshold after an E injection alone while there was a reduced tonic--clonic seizure threshold in the presence of both hormones (E + P) compared to the hormone treatment-matched group of saline-exposed females. In control females, in low magnesium medium in vitro, the development of two types of epileptiform activity (seizure-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. The present data demonstrate that the anticonvulsant effects of P on seizure susceptibility requires the presence of E. Furthermore, prenatal morphine exposure alters ovarian steroid hormone-regulated seizure susceptibility.
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. velisek@aecom.yu.edu
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Velísek
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Velísková
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Moshé
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Vathy
D000818:Animals; D003292:Convulsants; D004198:Disease Susceptibility; D018728:Entorhinal Cortex / Q000378:metabolism; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005481:Flurothyl; D008274:Magnesium / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010052:Ovariectomy; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D012640:Seizures / Q000139:chemically induced*
D003292:Convulsants; D004967:Estrogens; D009294:Narcotics; D011374:Progesterone; D009020:Morphine; D005481:Flurothyl; D008274:Magnesium