Role of Cotinine in Nicotine Use Disorders

摘要/描述 当前项目的主要目标是了解可替宁（COT）的奖励相关作用， 尼古丁 (NIC) 的主要代谢物及其在 NIC 使用障碍发展中的潜在作用。长- 术语目标是更好地理解 NIC 强化中的 COT 相关机制，并提供 针对 COT 作用的研究的基本原理，以促进未来开发辅助吸烟的新疗法 停止。总体假设是 COT 在 NIC 滥用的发展中发挥着重要作用 和成瘾通过多种机制结合，包括其自身的强化和渴望-/复发- 类似效应、这些效应涉及的独特机制、其与 NIC 的相互作用以促进 强化和渴望/复发样效果。涵盖行为学的多学科方法 该项目将采用神经科学和神经化学。因此，目标 1 将决定 与 NIC 相比，COT 与奖励相关的行为和神经化学效应。目标2将 确定参与增强效应的机制的潜在相似性或差异 COT 与 NIC。目标 3 将研究 COT 和 NIC 在促进 加固。目标 4 将研究 COT 及其类似渴望/复发的特性 与 NIC 相互作用，利用恢复模型促进渴望/复发样效应。潜力 COT 行为中的性别差异也将受到检查。这是一个非常新颖的项目。信息 所取得的成果不仅会显着增加我们对 COT 相关机制的理解 网卡加固和网卡使用障碍的发展，更凸显了其重要性 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.