Improving an animal model of tobacco addiction

改进烟草成瘾的动物模型

• 批准号: 7085997
• 负责人: JENNIFER M KULAK
• 金额: $ 6.85万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-10 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7085997
• 关键词: dopamine; model; nicotine; smoking; tobacco; tobacco abuse

DESCRIPTION (provided by applicant): Current animal models of nicotine addiction may not accurately reflect the biophysical changes that occur in the dopaminergic system and that may be associated with tobacco addiction. This proposal is designed to address a specific concern in regards to studies of tobacco addiction: the effects of multiple smoke constituents on the dopaminergic system (which is primarily involved in tobacco addiction). Current models of tobacco addiction focus solely on chronic nicotine administration and have not included other bioactive components of cigarette smoke, such as monoamine oxidase B (MAO-B) inhibitors, that are potent modulators of dopaminergic function. This is a potentially serious oversight since MAO-B inhibitors are present in significant amounts in cigarette smoke, along with nicotine. The research proposed in this application is designed to examine the effects of chronic nicotine administration in combination with chronic MAO-B inhibition in the mouse brain. Specific aim 1 is designed to study the extent to which chronic exposure to nicotine and an MAO-B inhibitor affects the dopaminergic system in young adult animals (by measuring dopamine & metabolite levels, MAO-B activity, tyrosine hydroxylase protein and mRNA expression, and dopamine transporter expression) and nicotinic acetylcholine receptor(nAChR) expression. Specific aim 2 studies are designed to examine the extent to which changes that occur in the neuronal dopaminergic and nAChR systems effects function of these systems. Thus, specific aim 2 studies will examine the effects of chronic nicotine and MAO-B inhibitor exposure, singly and in combination, on dopamine uptake and nicotine-evoked dopamine release. This proposal is designed to establish a more physiologically accurate model for tobacco addiction. Relevance: The effects of tobacco smoking on public health are well known. Unfortunately, current methods to treat tobacco addiction are not always successful. This project will investigate a model for smoking that may more accurately reflect the changes in the brain seen with tobacco addiction and may provide an improved research model for smoking cessation.

描述（由申请人提供）：当前的尼古丁成瘾动物模型可能无法准确反映多巴胺能系统中发生的生物物理变化，并且可能与烟草成瘾有关。该建议旨在解决有关烟草成瘾研究的特定问题：多种烟雾成分对多巴胺能系统的影响（主要参与烟草成瘾）。当前的烟草成瘾模型仅着眼于慢性尼古丁的给药，并且不包括香烟烟雾的其他生物活性成分，例如单胺氧化酶B（MAO-B）抑制剂，这些抑制剂是多巴胺能功能的有效调节剂。这是一种潜在的严重监督，因为MAO-B抑制剂与尼古丁一起出现了大量的香烟烟雾。本应用中提出的研究旨在检查慢性尼古丁给药与小鼠大脑中慢性MAO-B抑制作用的影响。特定目标1旨在研究慢性暴露于尼古丁和MAO-B抑制剂的程度，影响年轻动物的多巴胺能系统（通过测量多巴胺和代谢物水平，MAO-B活性，MAO-B活性，酪氨酸羟化酶蛋白质和mRNA蛋白质和mRNA表达，以及多巴胺转运剂表达）和多巴胺转移表达）和否认乙酰基乙烯基因（Nicotinic actyl Chinciline Croceors）（NACCYLCHILCHOLINELCYLINELCYLINELCYLINELCYLINERINERRIN）（NACCYYLCYLINELCYLINELCYLINELCYLINERRINENRIN）。具体目标2研究旨在研究这些系统神经元多巴胺能和NACHR系统影响功能的变化的程度。因此，具体目标2研究将检查慢性尼古丁和MAO-B抑制剂暴露，单独和结合，对多巴胺摄取和尼古丁诱发的多巴胺释放的影响。该建议旨在为烟草成瘾建立更精确的模型。相关性：众所周知，吸烟对公共卫生的影响。不幸的是，当前治疗烟草成瘾的方法并不总是成功的。该项目将调查一种吸烟模型，该模型可能更准确地反映了烟草成瘾所看到的大脑变化，并可能为戒烟提供改进的研究模型。