Schindler C J, Slamberová R, Vathy I
Department of Neuroscience, Albert Einstein College of Medicine, Ullmann 111, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Psychoneuroendocrinology. 2003 Apr;28(3):348-63. doi: 10.1016/s0306-4530(02)00027-6.
Prenatal morphine exposure (5-10 mg/kg twice daily on gestation days 11-18) can adversely affect neurological development, including seizure susceptibility. The present study examines the effects of prenatal morphine exposure on seizure susceptibility to the GABA antagonist and convulsant bicuculline and GABA(A) alpha(1) receptor mRNA in the substantia nigra (SN) of female rats. The results demonstrate that prenatally morphine-exposed ovariectomized (OVX) females and OVX females with estradiol benzoate (EB) replacement have an increased latency to seizure onset compared to controls. In addition, prenatal morphine exposure decreases the area covered by grains of GABA(A) alpha(1) receptor mRNA in the anterior SN in both OVX and EB+progesterone (P)-treated groups, and decreases the number of GABA(A) alpha(1) receptor mRNA-labeled cells/field in EB females. Furthermore, prenatally morphine- and saline-exposed EB and EB+P females had decreased GABA(A) alpha(1) receptor mRNA-labeled cells/field in the anterior SN compared to OVX animals of the same prenatal exposure. These results demonstrate that the long term effects of prenatal morphine exposure in female rats is dependent on their hormonal status, and suggest that seizure susceptibility may be altered via neuropharmacological changes in the GABA system in the SN.
产前吗啡暴露（在妊娠第11 - 18天每天两次，每次5 - 10毫克/千克）会对神经发育产生不利影响，包括癫痫易感性。本研究考察了产前吗啡暴露对雌性大鼠黑质中γ-氨基丁酸（GABA）拮抗剂和惊厥剂荷包牡丹碱的癫痫易感性以及GABA(A)α(1)受体信使核糖核酸（mRNA）的影响。结果表明，与对照组相比，产前暴露于吗啡的去卵巢（OVX）雌性大鼠以及接受苯甲酸雌二醇（EB）替代治疗的去卵巢雌性大鼠癫痫发作起始潜伏期延长。此外，在去卵巢组和接受EB + 孕酮（P）治疗的组中，产前吗啡暴露均减少了黑质前部GABA(A)α(1)受体mRNA颗粒覆盖的面积，并且减少了EB雌性大鼠中GABA(A)α(1)受体mRNA标记细胞/视野的数量。此外，与相同产前暴露的去卵巢动物相比，产前暴露于吗啡和生理盐水的EB及EB + P雌性大鼠黑质前部GABA(A)α(1)受体mRNA标记细胞/视野减少。这些结果表明，产前吗啡暴露对雌性大鼠的长期影响取决于其激素状态，并提示癫痫易感性可能通过黑质中GABA系统的神经药理学变化而改变。
