EFFECTS OF PRENATAL NICOTINE EXPOSURE ON BRAIN N-ACHR

怀孕的结果是不利的影响，母亲使用烟草 产品.宫内香烟烟雾暴露引起的畸变 从出生体重的减少到突发性心脏病的发生率的增加， 婴儿死亡综合症神经心理障碍，包括注意力 缺陷障碍和运动机能亢进在儿童中也更为普遍 母亲在怀孕期间吸烟。 虽然烟草烟雾 含有许多化合物，尼古丁被认为是主要的致畸剂。 对怀孕啮齿动物给予尼古丁会导致发育和 与人类吸烟者报告的行为障碍相似。 中枢神经系统中的烟碱胆碱能受体（nAChr） 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， 调节大脑的成熟。 拟议的研究将确定nAChr的发育模式 使用定量放射自显影术测定小鼠脑中的结合。尼古丁和 α-银环蛇毒素结合将在离散的脑位点中测量，使用 各种妊娠期和产后年龄的动物。信使RNA是 将在相邻的脑切片上检查脑nAChr编码， 定量原位杂交组织化学在子宫内的影响 尼古丁暴露对受体和mRNA发育发生率的影响 也将被调查。 尼古丁将长期给予 雌性小鼠通过饮水溶液。这种方法产生的应力很小 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胎儿对尼古丁敏感性的影响 尼古丁将通过一系列测试在后代中进行测试， 包括声音惊吓反应、旷场活动和身体 温度调节据预测，产前尼古丁暴露 会改变后代大脑中nAChr的数量;因此， 必须解决这些受体的功能状态。离子通量测定 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。纹状体组织将用于 测量尼古丁刺激的多巴胺释放;铷（K+示踪剂） 通量将用于测量其他脑中nAChr的功能反应 地区这些实验将提供重要的信息， 产前尼古丁暴露对脑发育的影响 烟碱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.