Role of Calcineurin in Nicotine Effects in Rats

描述（由申请人提供）：在美国，与吸烟相关的死亡人数每年超过44万人，然而仅在美国就有4620万吸烟者（CDC, 2004）。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强化的机制至关重要。动物反复服用尼古丁会导致行为改变，如运动敏化和条件性位置偏好，这被认为反映了尼古丁的强化特性。此外，尼古丁管理调节神经元活动，神经递质释放和下游信号在中脑边缘多巴胺系统，特别是在腹侧被盖区（VTA）和伏隔核。钙依赖蛋白磷酸酶，钙调神经磷酸酶，也调节许多与尼古丁成瘾有关的信号过程。因此，了解钙调磷酸酶在尼古丁介导的行为和神经化学可塑性中的作用是很重要的。本实验将1)确定VTA钙调磷酸酶活性对慢性尼古丁诱导的运动敏化的贡献，2)表征VTA钙调磷酸酶在尼古丁介导的信号通路中的作用。

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.