Circadian Variations in Nicotine Sensitivity in Mice

小鼠尼古丁敏感性的昼夜节律变化

基本信息

批准号：
7477295
负责人：
JERRY A STITZEL
金额：
$ 18.56万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2010-05-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): In the United States, the use of tobacco products is responsible for over 450,000 premature deaths per year (about 20% of all premature deaths) and accounts for around $100 billion dollars per year in health care costs. Despite these facts, approximately 25% of adults in the United States continue to smoke. Typically, however, even heavy smokers can abstain from smoking during the normal sleep cycle and wake no more frequently during the night than do non-smokers. This observation suggests that there may be circadian patterns in which craving for nicotine is reduced at night. In support of this possibility, recent studies have demonstrated that sensitivity to drugs of abuse is generally reduced at night as well as altered by mutations in genes that regulate the circadian clock. In addition, melatonin, a hormone whose synthesis peaks at night, decreases craving in abstinent smokers and reduces sensitivity to the rewarding properties of some drugs of abuse in rodents. Despite this information, very little research has been done to assess circadian variations in sensitivity to nicotine. In the experiments outlined in this proposal, we will perform exploratory studies in mice in order to define the circadian pattern of sensitivity to the acute effects of nicotine. We also will examine whether any identified variation in sensitivity to nicotine is associated with circadian variations in melatonin synthesis, nicotinic receptor expression and/or nicotine metabolism. Finally, we will determine whether melatonin signaling through melatonin receptors is required for circadian variations in nicotine sensitivity, nicotinic receptor expression and nicotine metabolism. These studies will identify time points, mouse strains and potential mechanisms that will guide future studies to understand the mechanisms that regulate altered sensitivity to nicotine over the course of the circadian cycle. Such knowledge may provide novel insights into the neurobiology of nicotine addiction. to public health: Understanding the role of daily variations in nicotine sensitivity and the potential role of melatonin on regulating these daily variations in nicotine sensitivity may provide insight into why smokers typically can sleep through the night without the need for a cigarette. This knowledge would be extremely useful for the development of better methods to treat nicotine addiction.

描述（由申请人提供）：在美国，使用烟草产品每年造成450,000多人的早期死亡（约占所有早期死亡的20％），每年约占1000亿美元的医疗保健费用。尽管有这些事实，美国约有25％的成年人继续吸烟。但是，通常情况下，即使吸烟者也可以在正常的睡眠周期中戒烟，而在夜间，醒来的频率也不是非吸烟者。该观察结果表明，可能有昼夜节律渴望在夜间减少尼古丁的模式。为了支持这种可能性，最近的研究表明，对滥用药物的敏感性通常会在夜间降低，并因调节昼夜节律时钟的基因突变而改变。此外，褪黑激素是一种夜间合成峰值的激素，降低了戒烟者的渴望，并降低了对啮齿动物中某些滥用药物的奖励性能的敏感性。尽管有这些信息，但很少进行研究来评估昼夜节律对尼古丁的敏感性变化。在该提案中概述的实验中，我们将在小鼠中进行探索性研究，以定义昼夜节律对尼古丁急性影响的敏感性。我们还将检查对尼古丁敏感性的任何鉴定的变化是否与褪黑激素合成，烟碱受体表达和/或尼古丁代谢的昼夜节律变化有关。最后，我们将确定是否需要通过褪黑激素受体的褪黑激素信号传导昼夜节律敏感性，烟碱受体表达和尼古丁代谢中的昼夜节律。这些研究将确定时间点，小鼠菌株和潜在的机制，这些机制将指导未来的研究以了解调节昼夜节律过程中对尼古丁敏感性改变的机制。这种知识可能会提供对尼古丁成瘾神经生物学的新颖见解。对公共卫生：了解日常变化在尼古丁敏感性中的作用以及褪黑激素对调节尼古丁敏感性的每日变化的潜在作用，可以洞悉为什么吸烟者通常可以整夜不需要香烟就可以入睡。这些知识对于开发更好的方法来治疗尼古丁成瘾将非常有用。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice.

通过对 Chrna7 无效突变小鼠的研究，补充与 α7 烟碱受体相关的妊娠期胆碱可长期改善感觉抑制。

DOI：
10.1016/j.brainres.2014.01.022
发表时间：
2014-03-13
期刊：
BRAIN RESEARCH
影响因子：
2.9
作者：
Stevens, Karen E.;Choo, Kevin S.;Stitzel, Jerry A.;Marks, Michael J.;Adams, Catherine E.
通讯作者：
Adams, Catherine E.