Rogel-Fuchs Y, Newman M E, Trombka D, Zahalka E A, Yanai J
Melvin A. and Eleanor Ross Laboratory for Studies in Neural Birth Defects, Department of Anatomy and Embryology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Brain Res Bull. 1992 Jul;29(1):1-6. doi: 10.1016/0361-9230(92)90002-f.
Mice were exposed to phenobarbital (PhB) prenatally and neonatally. Prenatal exposure was accomplished by feeding the mother PhB (3 g/kg milled food) on gestation days 9-18. Neonatal exposure was accomplished by daily injections of 50 mg/kg sodium PhB directly to the pups on days 2-21. Long-term biochemical alterations in the pre- and postsynaptic septohippocampal system, as well as related behavioral deficits, were assessed in the treated animals. Significant increase in B(max) values for binding of [3H]QNB to muscarinic cholinergic receptors was obtained on both ages 22 and 50 in prenatally (40-90%, respectively, p less than 0.001) and neonatally exposed (58-89%, p less than 0.001) mice whereas Kd remained normal. Similarly, a significant increase of inositol phosphate (IP) formation in response to carbachol was found after both prenatal and neonatal exposure to PhB (p less than 0.05). No alterations in choline acetyltransferase (ChAT) activity were observed in the prenatally or neonatally treated animals. The early exposed mice showed deficits in the performance in Morris water maze, a behavior related to the septohippocampal pathway. The results suggest that early exposure to PhB induces alterations in postsynaptic components of the hippocampal cholinergic system and concomitantly to impairment in hippocampus-related behavior.
小鼠在产前和新生期暴露于苯巴比妥（PhB）。产前暴露是通过在妊娠第9至18天给母鼠喂食PhB（3 g/kg磨碎食物）来实现的。新生期暴露是通过在第2至21天每天给幼崽直接注射50 mg/kg苯巴比妥钠来实现的。对经处理的动物评估了突触前和突触后隔海马系统的长期生化改变以及相关的行为缺陷。在产前（分别为40 - 90%，p < 0.001）和新生期暴露（58 - 89%，p < 0.001）的小鼠中，在22日龄和50日龄时，[3H]QNB与毒蕈碱胆碱能受体结合的B(max)值均显著增加，而Kd保持正常。同样，在产前和新生期暴露于PhB后，发现对卡巴胆碱的肌醇磷酸（IP）形成显著增加（p < 0.05）。在产前或新生期处理的动物中未观察到胆碱乙酰转移酶（ChAT）活性的改变。早期暴露的小鼠在莫里斯水迷宫中的表现存在缺陷，这是一种与隔海马通路相关的行为。结果表明，早期暴露于PhB会诱导海马胆碱能系统突触后成分的改变，并伴随与海马相关行为的损害。
