EFFECTS OF NICOTINE ON PROCESSES MEDIATED BY THE RETICULAR ACTIVATING SYSTEM

尼古丁对网状激活系统介导的过程的影响

• 批准号: 8168086
• 负责人: Roger A Buchanan
• 金额: $ 14.06万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-19 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168086
• 关键词: Accounting; Affect; Agonist; Animal Experiments; Animals; Anti-Anxiety Agents; Arousal; Attention; Auditory Evoked Potentials; Cell Nucleus; Computer Retrieval of Information on Scientific Projects Database; Development; Dose; Estrogens; Exposure to; Female; Funding; Gonadal Steroid Hormones; Grant; Hippocampus (Brain); Injection of therapeutic agent; Institution; Maternal Exposure; Measures; Mediating; Modification; Neurons; Nicotine; Nicotinic Receptors; Output; Pregnancy; Process; Rattus; Research; Research Personnel; Resources; Role; Sensory; Series; Site; Sleep; Source; System; Testing; United States National Institutes of Health; Women' s Role; arm; cholinergic; cigarette smoking; design; in utero; in vivo; novel; response

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在一系列的动物实验中，我们发现了尼古丁的一个潜在的新作用部位。 我们已经证明，全身注射尼古丁导致网状激活系统（RAS）产生的睡眠状态依赖性、顶点记录的P13中潜伏期听觉诱发电位的振幅呈剂量依赖性降低，将烟碱受体拮抗剂局部注射到RAS的胆碱能臂，（脚桥核[PPN]）阻断全身尼古丁对P13电位的影响（唤醒水平的测量），并且将烟碱受体激动剂局部注射到PPN中也导致P13电位幅度的降低，通过PPN注射烟碱受体拮抗剂阻断该作用。尼古丁也降低了海马N40电位，尽管这些作用不受PPN中拮抗剂或激动剂注射的影响。香烟烟雾中尼古丁的警觉，自由移动的动物P13中潜伏期听觉诱发电位（MAEP）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种潜在的机制，并对了解尼古丁在正常和病理条件下的作用具有重要意义。目的1-3将检验NIC对体内PPN神经元具有直接作用的假设，这解释了NIC对唤醒的一些影响。目的1将描述NIC对重复感觉输入的唤醒和习惯化反应的影响。 在目标2中，我们将确定暴露于香烟烟雾对重复感觉输入的唤醒和习惯化的影响。 目的3将描述母亲在怀孕期间暴露于香烟烟雾对体内PPN介导的反应的影响。 目的4和目的5旨在检验PPN输出被雌性性激素改变以及这些改变影响雌性动物对NIC的反应的假设。 目的4研究雌性激素在调节雌性大鼠PPN介导的反应中的作用。 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，检查子宫内尼古丁暴露对随后发展的RAS介导的活动相关的唤醒和注意力的影响。