Role of Cotinine in Nicotine Use Disorders

可替宁在尼古丁使用障碍中的作用

• 批准号: 10120071
• 负责人: Zheng-Ming Ding
• 金额: $ 35.62万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10120071
• 关键词: Address; Attention; Behavior; Behavioral; Blood; Brain; Bupropion; Cessation of life; Cotinine; Cues; Data; Developed Countries; Development; Dopamine; Dose; Effectiveness; FDA approved; Female; Future; Goals; Half-Life; Individual; Intravenous; Knowledge; Light; Maintenance; Mecamylamine; Mediating; Modeling; Molecular Target; Neurosciences; Nicotine; Nicotine Dependence; Nicotine Use Disorder; Nicotinic Receptors; Pharmaceutical Preparations; Pharmacology; Pilot Projects; Plasma; Play; Procedures; Property; Psychological reinforcement; Rattus; Relapse; Reporting; Research; Rewards; Role; Self Administration; Sex Differences; Stress; Targeted Research; cigarette smoking; craving; drug of abuse; extracellular; insight; interdisciplinary approach; male; mesolimbic system; neurochemistry; new therapeutic target; nicotine abuse; nicotine seeking behavior; nicotine use; novel; novel therapeutics; premature; smoking cessation; therapeutic target; varenicline

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.

摘要/描述 本项目的主要目的是了解可替宁（COT）的奖励相关作用， 尼古丁的主要代谢物（NIC），及其在NIC使用障碍的发展中的潜在作用。很长的- 长期目标是更好地理解NIC强化中COT相关机制，并提供 针对COT作用的研究的基本原理，用于未来开发辅助吸烟的新疗法 停止总体假设是COT在NIC滥用的发展中起着重要作用 和成瘾通过一系列机制，包括其自身的强化和渴望-/复发- 如影响，在这些影响中涉及的独特机制，它与NIC的相互作用，以促进 增强和渴望-/复发样的效果。一种多学科的方法，包括行为 神经科学和神经化学将在这个项目中使用。因此，目标1将决定 与NIC相比，COT的奖励相关行为和神经化学作用。aim 2将 确定参与强化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的渴望/复发样特性及其对人的影响。 与NIC的相互作用，以促进渴望/复发样作用使用恢复模型。潜在 COT行动中的性别差异也将被研究。这是一个非常新颖的项目。信息 这不仅将大大增加我们对COT相关机制的理解， NIC的强化和NIC使用障碍的发展，也凸显了 将COT作为治疗NIC使用障碍的新策略。