Velísek L, Velísková J, Moshé S L, Vathy I
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Brain Res. 1998 Jun 15;796(1-2):247-56. doi: 10.1016/s0006-8993(98)00367-9.
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.
本研究在体内氟烷惊厥模型以及体外脑片低镁诱导的癫痫样活动中，检测了产前暴露于吗啡和生理盐水的成年雌性大鼠癫痫易感性的卵巢激素调节。所有雌性大鼠均接受卵巢子宫切除术（OVX）；部分大鼠接受雌激素（E）或孕酮（P）替代治疗，而其他大鼠则依次注射E + P。在产前接受生理盐水处理的对照雌性大鼠中，与OVX对照相比，在两种激素（E + P）存在的情况下，氟烷诱导的阵挛性惊厥阈值升高（抗惊厥作用）。在暴露于吗啡的雌性大鼠中，单独注射E后氟烷诱导的阵挛性惊厥阈值升高，而与激素治疗匹配的生理盐水暴露雌性大鼠组相比，在两种激素（E + P）存在的情况下，强直-阵挛性惊厥阈值降低。在对照雌性大鼠中，在体外低镁培养基中，两种类型的癫痫样活动（癫痫样事件和短放电状态）的发展不受不同激素条件的影响。然而，与注射E的对照雌性大鼠相比，产前吗啡暴露抑制了注射E的雌性大鼠中两种类型癫痫样活动的发展。本研究数据表明，P对癫痫易感性的抗惊厥作用需要E的存在。此外，产前吗啡暴露会改变卵巢甾体激素调节的癫痫易感性。
