Noble E P, Ritchie T
Neuropsychiatric Institute, University of California, Los Angeles 90024-1759.
Life Sci. 1989;45(9):803-10. doi: 10.1016/0024-3205(89)90173-2.
Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross-fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with [3H] inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of [3H]inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggest that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers.
孕期长期摄入酒精会导致胎儿酒精综合征（FAS），这是一种以学习障碍为特征的疾病。通过给怀孕的斯普拉格-道利大鼠喂食含35%乙醇热量的液体饲料建立FAS大鼠模型（E组），而另一组则配对喂食不含乙醇的等热量液体饲料（P组）。第三组怀孕母鼠自由摄食实验室饲料（C组）。分娩时，E组和P组的幼崽由C组母鼠交叉寄养，所有组均喂食实验室饲料。成年后，处死雄性后代，海马体和前额叶皮质切片用[3H]肌醇预先标记。通过测量在LiCl存在下，各种兴奋性氨基酸（EAA）受体激活后[3H]肌醇磷酸的积累来测定磷酸肌醇（PI）水解。在海马体切片中，与P组和C组动物相比，E组中鹅膏蕈氨酸和quisqualate诱导的PI水解减少。此外，在P组和C组动物中明显的N-甲基-D-天冬氨酸（NMDA）对卡巴胆碱诱导的PI水解的抑制作用，在E组动物的海马体中完全消失。相反，在前额叶皮质中，即使在E组动物中，NMDA的这种抑制作用仍然存在。证据表明，产前乙醇暴露会改变海马体中第二信使生成过程中EAA受体的活性。
