Role of Cotinine in Nicotine Use Disorders

摘要/描述 本项目的主要目标是了解可替宁(CoT)的奖赏相关行为， 尼古丁的主要代谢物(NIC)及其在NIC使用障碍发展中的潜在作用。长的- 学期目标是更好地了解NIC加固中与COT相关的机制，并提供 针对COT作用的研究为未来开发新的辅助吸烟疗法提供理论基础 停止。最重要的假设是COT在NIC滥用的发展中起着重要的作用 和成瘾通过一系列机制的组合，包括其自身的强化和渴望-/复发- 相似效应，参与这些效应的独特机制，其与网卡的互动促进 强化和渴求--/旧病复发--类效应。包括行为学在内的多学科方法 神经科学和神经化学将被运用在这个项目中。因此，目标1将决定 与NIC相比，COT的奖赏相关行为和神经化学效应。AIM2将 确定增强作用所涉及的机制的潜在相似性或差异 COT VS NIC。目标3将研究COT和NIC之间在Promote中的潜在交互作用 增援。和目标4将调查婴儿床的渴求/复发的性质及其 使用恢复模型与NIC进行交互以促进类似渴望/复发的效果。潜力 此外，还将研究考特行动中的性别差异。这是一个非常新奇的项目。信息 所取得的成果不仅将显著增加我们对COT相关机制的理解 网卡的加强和网卡使用障碍的发展，也凸显了网卡的重要性 将COT作为治疗NIC使用障碍的新策略。

ABSTRACT/DESCRIPTION The major objective of the current project is to understand the reward-related actions of cotinine (COT), the major metabolite of nicotine (NIC), and its potential role in the development of NIC use disorder. The long- term goal is to provide a better understanding of COT-related mechanisms in NIC reinforcement and provide rationale for research targeting the actions of COT for future development of new therapies for aiding smoking cessation. The overarching hypothesis is that COT plays an important role in the development of NIC abuse and addiction through a combination of mechanisms, including its own reinforcing and craving-/relapse- like effects, unique mechanisms involved in these effects, its interactions with NIC to promote reinforcing and craving-/relapse-like effects. A multidisciplinary approach encompassing behavioral neuroscience and neurochemistry will be employed in this project. Thus, Aim 1 will determine the reward-related behavioral and neurochemical effects of COT as compared to NIC. Aim2 will determine potential similarities or differences in mechanisms involved in the reinforcing effects of COT vs NIC. Aim 3 will examine potential interactions between COT and NIC in promote reinforcement. And Aim 4 will investigate the craving-/relapse-like properties of COT and its interactions with NIC to promote craving-/relapse-like effects using reinstatement models. Potential sex differences in COT's actions will also be examined. This is a highly novel project. Information attained will not only significantly increase our understanding of COT-related mechanisms underlying NIC reinforcement and the development of NIC use disorders, but also highlight the importance of targeting COT as a new strategy for treating NIC use disorders.