Role of striatal pathways in learning with nicotine stimulus

纹状体通路在尼古丁刺激学习中的作用

• 批准号: 10514350
• 负责人: Sergios Charntikov
• 金额: $ 44.63万
• 依托单位: UNIVERSITY OF NEW HAMPSHIRE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10514350
• 关键词: Absence of pain sensation; Afferent Pathways; Alcohols; Anterior; Applications Grants; Area; Association Learning; Awareness; Biological; Cessation of life; Clinical; Clinical Research; Cocaine; Complex; Corpus striatum structure; Data; Dimensions; Disinhibition; Dopamine D1 Receptor; Dopamine D2 Receptor; Dose; Efferent Pathways; Environment; Event; Excitotoxic lesion; Food; Funding; Genetic; Globus Pallidus; Goals; Grant; Institution; Laboratories; Learning; Methamphetamine; Modeling; Morphology; Names; Nature; Neurobiology; Nicotine; Nicotine Dependence; Output; Pathway interactions; Pharmaceutical Preparations; Pharmacology; Positioning Attribute; Prefrontal Cortex; Preparation; Process; Property; Public Health; Publishing; Research; Research Personnel; Rewards; Role; Saline; Science; Self Administration; Site; Stimulant; Stimulus; Substantia nigra structure; System; Testing; Tobacco use; Variant; Virus; Work; attenuation; behavioral response; experimental study; field study; genetic approach; hands on research; improved; neural; neurobiological mechanism; nicotine reward; nicotine self-administration; nicotine use; peer; pharmacologic; pre-clinical; pre-clinical research; programs; psychostimulant; putamen; receptor; reinforcer; response; theories; tobacco products; undergraduate student; virtual

Project Summary Nicotine is a mild stimulant when compared to other stimulants like cocaine or methamphetamine. Indeed, responding for nicotine in preclinical self-administration studies is only marginally higher than responding for saline and is often insensitive to variation in nicotine dose. The fact that nicotine is a weak primary reinforcer is somewhat incongruent with the fact that it is one of the most abused substances. The wide use of nicotine products has been attributed to the complex nature of nicotine reward that involves genetic, biological, learning, and pharmacological dimensions, to name a few. The pharmacological effects of nicotine can serve as an interoceptive stimulus (CS) that can come into association with other reinforcing events in the environment (US; e.g., food, alcohol, work breaks, peer interaction) and through associative processes can acquire additional properties that likely contribute to perpetuation of nicotine use. Previous studies show that dorsomedial caudate-putamen (dmCPu) is functionally involved in learning with nicotine stimulus. We also know that anterior (a-) and posterior (p-) dmCPu are differentially involved in various stages of that learning. Both a- and p-dmCPu receive excitatory input from the prefrontal cortex and provide inhibitory output to substantia nigra pars reticulata/globus pallidus internus complex (SNr/GPi) via direct (D1 driven) or indirect (D2 driven) pathways. What we do not know is how these afferent and efferent connections to dmCPu contribute to learning with nicotine stimulus. Thus, the overall objective of this application is to investigate the functional involvement of afferent and efferent connections to dmCPu in learning with nicotine stimulus using pathways- specific chemogenetic approach. The experiments proposed in this application will be the first to identify immediate circuitry involved in associative learning with any drug state. A better understanding of neurobiological mechanisms involved in associative learning with nicotine stimulus may open new avenues in preclinical or clinical research investigating the neural underpinnings of nicotine dependence.

项目摘要 与其他兴奋剂（如可卡因或甲基苯丙胺）相比，尼古丁是一种温和的刺激剂。的确， 在临床前自我管理研究中对尼古丁的反应仅比响应 盐水，通常对尼古丁剂量变化不敏感。尼古丁是弱的主要增强剂的事实是 它是最虐待物质之一的事实有些不一致。尼古丁的广泛使用 产品归因于尼古丁奖励的复杂性，涉及遗传，生物学， 学习和药理学维度等等。尼古丁的药理作用可以作为 可以与环境中其他强化事件相关的互感刺激（CS） （美国；例如，食物，酒精，工作休息，同伴互动）以及通过关联过程可以获取更多 可能有助于尼古丁使用的属性。先前的研究表明背侧 尾状药物（DMCPU）在功能上与尼古丁刺激一起学习。我们也知道 前（A-）和后（p-）DMCPU在该学习的各个阶段都差异化。 A-和 p-DMCPU从前额叶皮层接收兴奋性输入，并为黑质提供抑制作用 通过直接（D1驱动）或间接（D2驱动），PARS Eticulata/Globus pallidus intrus Interus Complex（SNR/GPI） 途径。我们不知道的是与DMCPU的这些传入和传出的联系有助于 用尼古丁刺激学习。因此，该应用的总体目的是研究功能 使用途径与尼古丁刺激一起学习传入和传统连接与DMCPU的参与 - 特定的化学发生方法。本应用程序中提出的实验将是第一个确定的实验 与任何药物状态有关的关联学习涉及的直接电路。更好地理解 与尼古丁刺激相关学习涉及的神经生物学机制可能会在 临床前或临床研究研究了尼古丁依赖性的神经基础。