EFFECTS OF PRENATAL NICOTINE EXPOSURE ON BRAIN N-ACHR

孕妇吸烟会对妊娠结局产生不利影响。 产品。宫内香烟烟雾暴露引起的畸变率 范围从出生体重的减少到突发疾病的发生率增加 婴儿死亡综合症。包括注意力在内的神经心理障碍 缺陷障碍和多动症在儿童中也更普遍。 她的母亲在怀孕期间吸烟。尽管烟草烟雾 含有多种化合物，尼古丁被认为是主要致畸物质。 给怀孕的啮齿动物注射尼古丁会导致发育和 与人类吸烟者报告的行为障碍类似的行为障碍。 中枢神经系统中的烟碱型胆碱能受体 调节尼古丁的行为和生理效应。这些 受体存在于胚胎发育的早期阶段，可能 调节大脑的成熟。 拟议的研究将确定nAChr的发展模式 用定量放射自显影技术研究小鼠脑内结合情况。尼古丁和 阿尔法-银环蛇毒素结合将在离散的大脑基因座上进行测量，使用 不同孕期和出生后年龄的动物。信使RNA‘s That 大脑nAChr的编码将在相邻的大脑切片上进行检查，使用 定量原位杂交组织化学。宫内妊娠的影响 尼古丁暴露对受体和mRNA发育发生率的影响 也将接受调查。尼古丁将长期服用于 雌性小鼠通过饮水剂灌胃。这种方法产生的压力很小。 并导致行为和大脑的显著变化 生物化学。产前尼古丁暴露对人对烟草敏感性的影响 尼古丁将在后代身上进行测试，使用一系列测试 包括声学惊吓反应、野外活动和身体 温度调节。据预测，产前接触尼古丁 会改变子代大脑中nAChr的数量；因此 这些受体的功能状态必须得到解决。离子通量分析 最近被开发用于评估对尼古丁的反应性 在生化水平上的刺激。纹状体组织将被用来 测量尼古丁刺激的多巴胺释放；Rb(K+的示踪剂) 通量将被用来测量其他大脑中nAChr的功能反应 地区。这些实验将提供有关 产前尼古丁暴露对脑发育的影响 尼古丁胆碱能系统和对尼古丁的反应性。

The outcome of pregnancy is adversely affected by maternal use of tobacco products. Aberrations produced by in utero exposure to cigarette smoke range from a reduction in birth weight to an increased incidence of sudden infant death syndrome. Neuropsychological disorders including attention deficit disorder and hyperkinesis are also more prevalent in children whose mothers smoked cigarettes during pregnancy. Although tobacco smoke contains many compounds, nicotine is considered the primary teratogen. Nicotine administration to pregnant rodents causes developmental and behavioral disorders that are similar to those reported for human smokers. Nicotinic cholinergic receptors (nAChr) in the central nervous system mediate the behavioral and physiological effects of nicotine. These receptors are present at early stages of embryonic development and may modulate the maturation of the brain. The proposed research will identify the developmental pattern of nAChr binding in mouse brain using quantitative autoradiography. Nicotine and alpha-bungarotoxin binding will be measured in discrete brain loci, using animals of various gestational and postnatal ages. Messenger RNA's that encode for brain nAChr will be examined on adjacent brain sections using quantitative in situ hybridization histochemistry. The effects of in utero nicotine exposure on the developmental incidence of the receptors and mRNA will also be investigated. Nicotine will be chronically administered to female mice via the drinking solution. This method produces little stress and results in significant changes in behavior as well as brain biochemistry. The effects of prenatal nicotine exposure on sensitivity to nicotine will be tested in the offspring using a battery of tests that includes acoustic startle response, open field activity and body temperature regulation. It is predicted that prenatal nicotine exposure will alter the number of brain nAChr in the progeny; therefore the functional status of these receptors must be addressed. Ion flux assays have recently been developed to assess responsiveness to nicotinic stimulation at the biochemical level. Striatal tissue will be used to measure nicotine-stimulated dopamine release; rubidium (a tracer for K+) flux will be used to measure functional responses of nAChr in other brain regions. These experiments will provide important information concerning the effects of prenatal nicotine exposure on the development of brain nicotinic cholinergic systems and responsiveness to nicotine.