Nicotine Exposure: Molecular to Behavioral Consequences

尼古丁暴露：分子行为后果

• 批准号: 7618706
• 负责人: Paul R Vezina
• 金额: $ 89.79万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7618706
• 关键词: Nicotine; Exposure; Molecular; Behavioral; Consequences

DESCRIPTION (provided by applicant): Tobacco use remains a major public health concern in the United States and abroad where it is a major factor in the initiation of illnesses leading to preventable death. Yet, despite such adverse consequences, the number of smokers continues to increase worldwide. Although considerable progress has been made in elucidating the neuronal mechanisms underlying several of the effects of nicotine, the active component of tobacco, the knowledge accumulated to date falls short of what is necessary to intervene successfully to reduce tobacco use. The experiments proposed in this program project will use a multi-disciplinary approach to assess the impact of repeated exposure to nicotine on nicotinic acetylcholine receptors (nAChRs), neuronal excitability and behavior. They have in common the goal of ultimately understanding how nicotine acts to initiate self-administration behaviors and how repeated exposure to nicotine produces changes that promote the continued expression of these behaviors. Nicotine produces its effects on motivated behavior by activating brain nAChRs. The ability of nicotine to up regulate these receptors can thus have a substantial impact on the ability of this drug to initiate such behaviors in animals subsequently re-exposed to it. Project 1 will aim to identify the molecular mechanisms underlying nicotine-induced up regulation of nAChRs and characterize this phenomenon in different brain regions of nicotine-exposed rats. As with other drugs of abuse, nicotine use relies in large part on its ability to increase midbrain dopamine transmission. Project 2 will characterize the effect of previous exposure to nicotine on the functional properties of nAChRs with access to these dopamine systems and assess their contribution to long-term potentiation of synapses onto dopamine cells. Repeated exposure to nicotine is known to lead to locomotor sensitization, yet little is known about how this effect is produced. Project 3 will identify the brain nAChR fields involved, characterize their role in the induction of sensitization of dopamine neuron reactivity and determine whether their repeated activation leads to increased motivation to self-administer nicotine.

烟草使用仍然是美国和国外的一个主要公共卫生问题，它是引发疾病的主要因素，导致可预防的死亡。然而，尽管有这些不利后果，全世界吸烟者的人数继续增加。虽然在阐明烟草的活性成分尼古丁的几种作用的神经机制方面取得了相当大的进展，但迄今为止积累的知识福尔斯还不足以成功地进行干预以减少烟草使用。该计划项目中提出的实验将使用多学科方法来评估重复暴露于尼古丁对烟碱乙酰胆碱受体（nAChR），神经元兴奋性和行为的影响。他们的共同目标是最终了解尼古丁如何启动自我给药行为，以及重复暴露于尼古丁如何产生促进这些行为持续表达的变化。尼古丁通过激活大脑nAChR对动机行为产生影响。尼古丁上调这些受体的能力，因此可以有一个实质性的影响，这种药物的能力，启动这种行为的动物随后重新暴露于it.Project 1的目的是确定尼古丁诱导的nAChRs上调的分子机制，并在不同的大脑区域尼古丁暴露大鼠这种现象的特点。与其他滥用药物一样，尼古丁的使用在很大程度上依赖于其增加中脑多巴胺传输的能力。项目2将描述先前暴露于尼古丁对nAChR功能特性的影响，并评估其对多巴胺细胞突触长时程增强的贡献。已知重复暴露于尼古丁会导致运动敏感化，但对这种效应如何产生知之甚少。项目3将确定所涉及的大脑nAChR区域，表征其在多巴胺神经元反应性敏化诱导中的作用，并确定其重复激活是否会导致自我给予尼古丁的动机增加。