EFFECTS OF NICOTINE ON PROCESSES MEDIATED BY THE RETICULAR ACTIVATING SYSTEM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在一系列动物实验中，我们已经确定了尼古丁潜在的新作用部位。我们已经证明，全身注射尼古丁导致由网状激活系统(RAS)产生的睡眠状态依赖的、顶点记录的P13中潜伏期听觉诱发电位的幅度随剂量的下降而下降，将尼古丁受体拮抗剂局部注射到RAS的胆碱能臂(脚桥核[PPN])可阻断全身尼古丁对P13电位(觉醒水平的衡量)的影响，局部向PPN注射尼古丁受体激动剂也导致P13电位的幅度下降，这种作用可被PPN注射尼古丁受体拮抗剂阻断。尼古丁也降低了海马N40电位，尽管这些作用不受PPN内注射拮抗剂或激动剂的影响。在香烟烟雾中注入尼古丁以提醒自由活动的动物对P13中潜伏期听觉诱发电位(MAEP)也有类似的影响。这些结果为解释尼古丁的抗焦虑作用提供了一个潜在的机制，并对理解尼古丁在正常和病理条件下的作用具有重要意义。AIMS 1-3将测试NIC对体内PPN神经元有直接作用的假设，这解释了NIC对唤醒的一些影响。目的1将描述NIC对重复感觉输入的反应的唤醒和习惯化的影响。在目标2中，我们将确定暴露在香烟烟雾中对重复感觉输入的唤醒和习服的影响。目的3研究孕妇孕期吸烟对PPN介导的体内反应的影响。AIMS 4和5的设计目的是测试PPN输出被雌性性激素改变的假设，以及这些改变影响雌性动物对NIC的反应。目的4研究雌性激素在调节PPN介导的雌性大鼠反应中的作用。目的5将确定雌激素在调节PPN介导的雌性大鼠对NIC的反应中的作用。这也提供了一个独特的机会来研究宫内尼古丁暴露对RAS介导的与唤醒和注意相关的活动的后续发展的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In a series of animal experiments, we have identified a potential novel site of action for nicotine. We have shown that systemic injection of nicotine led to a dose-dependent decrease in the amplitude of the sleep state-dependent, vertex recorded, P13 midlatency auditory evoked potential generated by the reticular activating system (RAS), that localized injections of a nicotinic receptor antagonist into the cholinergic arm of the RAS (the pedunculopontine nucleus [PPN]) blocked the effects of systemic nicotine on the P13 potential (a measure of level of arousal), and that localized injection of a nicotinic receptor agonist into the PPN also led to a decrease in the amplitude of the P13 potential, an effect blocked by PPN injection of a nicotinic receptor antagonist. Nicotine also decreased the hippocampal N40 potential although these effects were not affected by antagonist or agonist injections into the PPN. Nicotine administered in cigarette smoke to alert, free moving animals had similar effects on the P13 midlatency auditory evoked potential (MAEP). These results provide a potential mechanism for explaining the anxiolytic effects of nicotine and have important implications for understanding the effects of nicotine under normal and pathological conditions. Aims 1-3 will test the hypothesis that NIC has a direct action on PPN neurons in vivo that account for some of the effects of NIC on arousal. Aim 1 will characterize the effects of NIC on arousal and habituation of responses to repetitive sensory input. In Aim 2, we will determine the effects of exposure to cigarette smoke on arousal and habituation to repetitive sensory input. Aim 3 will characterize the effects of maternal exposure to cigarette smoke during pregnancy on PPN-mediated responses in vivo. Aims 4 and 5 are designed to test the hypothesis that PPN output is modified by female sex hormones and that these modifications affect female animals' responses to NIC. Aim 4 will characterize the role of female sex hormones in modulating PPN-mediated responses of female rats. Aim 5 will determine estrogen's role in modulating PPN-mediated responses of female rates to NIC. This also provides a unique opportunity to examine the effects of in utero nicotine exposure on the subsequent development of RAS-mediated activities related to arousal and attention.