Zahalka E H, Rehavi M, Newman M E, Yanai J
Department of Anatomy and Embryology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Psychopharmacology (Berl). 1995 Nov;122(1):44-50. doi: 10.1007/BF02246440.
Previous studies demonstrated postsynaptic septohippocampal cholinergic alterations after early exposure to phenobarbital. The present study was designed to ascertain possible corresponding presynaptic alterations while confirming the known behavioral deficits and extending previous findings on postsynaptic cholinergic alterations. Pregnant heterogeneous mice received milled mouse food containing 3 g/kg phenobarbital on gestation days 9-18. At age 50 days, [3H]hemicholinium-3 binding, which labels the presynaptic transporter for high affinity choline uptake, was increased in treated mice by 100% (P < 0.001). This change was not accompanied by a change in the affinity of the transporter to the ligand. Another group of offspring was tested for hippocampus-related behaviors. Consistent with our previous studies in the Morris maze, treated animals took longer to reach the platform in the place test as compared to control, and swam fewer times over the missing platform location in the spatial probe test. In the eight-arm maze, the treated offspring needed more entries than control to visit all the arms. In the spontaneous alternation test, the treated mice showed fewer alternations than controls. Biochemically, as in our previous results, prenatal phenobarbital exposure resulted in an increase in the degree of stimulation of inositol phosphate formation by carbachol (P < 0.05), an action presumed to occur at postsynaptic muscarinic receptors. While the present results show that the effect of a combination of raised K+ in the presence of physostigmine and carbachol was significantly greater in barbiturate-treated mice (P < 0.05), the action of K+ in the presence of physostigmine, but without carbachol, was not affected by the phenobarbital treatment. The results point to the uniqueness of outcome of early insults where alterations along nerve conduction cascades do not necessarily follow the common rules in that upregulation could simultaneously occur both pre- and post synaptically.
先前的研究表明，早期接触苯巴比妥后海马旁回胆碱能突触后发生改变。本研究旨在确定可能相应的突触前改变，同时确认已知的行为缺陷，并扩展先前关于突触后胆碱能改变的研究结果。怀孕的杂种小鼠在妊娠第9至18天接受含3 g/kg苯巴比妥的碾碎小鼠食物。在50日龄时，[3H]半胱氨酸-3结合（标记用于高亲和力胆碱摄取的突触前转运体）在经处理的小鼠中增加了100%（P < 0.001）。这种变化并未伴随着转运体与配体亲和力的改变。另一组后代接受了与海马相关行为的测试。与我们先前在莫里斯迷宫中的研究一致，与对照组相比，经处理的动物在位置测试中到达平台所需时间更长，并且在空间探测测试中在缺失平台位置上方游动的次数更少。在八臂迷宫中，经处理的后代比对照组需要更多的进入次数才能访问所有臂。在自发交替测试中，经处理的小鼠表现出的交替次数比对照组少。生化方面，与我们先前的结果一样，产前接触苯巴比妥导致卡巴胆碱刺激肌醇磷酸形成的程度增加（P < 0.05），这一作用推测发生在突触后毒蕈碱受体上。虽然目前的结果表明，在毒扁豆碱和卡巴胆碱存在下升高钾离子的联合作用在巴比妥酸盐处理的小鼠中显著更大（P < 0.05），但在毒扁豆碱存在但无卡巴胆碱时钾离子的作用不受苯巴比妥处理的影响。结果表明早期损伤结果的独特性，即沿着神经传导级联的改变不一定遵循共同规则，因为上调可同时发生在突触前和突触后。
