Role of Calcineurin in Nicotine Effects in Rats

钙调神经磷酸酶在大鼠尼古丁效应中的作用

• 批准号: 7112527
• 负责人: Nii A Addy
• 金额: $ 2.35万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7112527
• 关键词: Role; Calcineurin; Nicotine; Effects; Rats

DESCRIPTION (provided by applicant): Smoking related deaths in the US number over 440,000 per year and yet there are 46.2 million smokers in US alone (CDC, 2004). Nicotine is believed to be the primary addictive component of cigarettes, and thus it is critical to gain a better understanding of the mechanisms of nicotine reward and reinforcement. Repeated nicotine administration in animals leads to behavioral changes, such as locomotor sensitization and conditioned place preference, which are thought to reflect its reinforcing properties. In addition, nicotine administration modulates neuronal activity, neurotransmitter release and downstream signaling in the mesolimbic dopamine system, specifically in the ventral tegmental area (VTA) and nucleus accumbens. The calcium-dependent protein phosphatase, calcineurin, also modulates many of the signaling processes implicated in nicotine addiction. Thus, it is important to understand the role of calcineurin in nicotine- mediated behavioral and neurochemical plasticity. The proposed experiments will 1) determine the contribution of calcineurin activity in the VTA to chronic nicotine-induced locomotor sensitization and 2) characterize the role of VTA calcineurin in nicotine-mediated signaling pathways.

描述（由申请人提供）：美国每年440,000多人的吸烟与吸烟相关的死亡人数，但仅美国就有4620万吸烟者（CDC，2004年）。尼古丁被认为是香烟的主要成瘾成分，因此，更好地了解尼古丁奖励和增强机制至关重要。动物中反复的尼古丁给药会导致行为变化，例如运动敏化和条件的位置偏好，这被认为反映了其增强特性。此外，尼古丁给药可调节中唇多巴胺系统中的神经元活性，神经递质释放和下游信号传导，特别是在腹侧偏片区域（VTA）和八核中。钙依赖性蛋白磷酸酶钙调神经蛋白也调节了与尼古丁成瘾有关的许多信号传导过程。因此，重要的是要了解钙调蛋白在尼古丁介导的行为和神经化学可塑性中的作用。提出的实验将1）确定VTA中钙调蛋白活性对慢性尼古丁诱导的运动敏化的贡献，2）表征VTA钙调蛋白在尼古丁介导的信号传导途径中的作用。