Imaging Nicotine-induced behavioral sensitization with fMRI

使用功能磁共振成像对尼古丁诱导的行为过敏进行成像

• 批准号: 7795248
• 负责人: JEAN A KING
• 金额: $ 35.47万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795248
• 关键词: AMPA Receptors; Address; Affect; Agonist; Animals; Anterior; Behavioral; Brain; Brain region; Conscious; Data; Devices; Dose; Exposure to; Functional Magnetic Resonance Imaging; Globus Pallidus; Glutamate Receptor; Glutamates; Hippocampus (Brain); Human; Image; Individual; Knowledge; Magnetic Resonance Spectroscopy; Measures; Monoamine Oxidase Inhibitors; N-Methylaspartate; Neurons; Neurotransmitters; Nicotine; Nicotine Dependence; Nucleus Accumbens; Parahippocampal Gyrus; Pharmaceutical Preparations; Prefrontal Cortex; Rodent; Role; Signal Transduction; Structure; Techniques; Testing; Time; Translating; Ventral Tegmental Area; Visual Cortex; addiction; awake; behavioral sensitization; blood oxygen level dependent; cingulate gyrus; drug of abuse; improved; innovation; mortality; novel; receptor; relating to nervous system; response; tool; transmission process

DESCRIPTION (provided by applicant): Functional magnetic resonance imaging (fMRI) of the brain has improved our understanding of drugs of abuse. Progress in applying this approach to conscious animals has been slow because subjects must be immobile during imaging. We have invented a device that allows us to image rodents while awake, opening new opportunities to study brain function non-invasively over time. Repeated exposure to drugs of abuse evokes a progressive increase in locomotor stimulation, termed behavioral sensitization. It is thought that sensitization is central to addiction to drugs, including nicotine. This resubmission addresses two potentially important observations about nicotine sensitization. First, it can be imaged with fMRI, allowing identification of the brain structures involved. The role of individual neurotransmitters in sensitization can be evaluated through the administration of selected receptor agonists to sensitized animals during imaging. Our preliminary data indicate that fMRI can be used to determine the role in sensitization to glutamate receptors in various brain regions. The aims of this proposal are 1) to determine if the administration of nicotine to sensitized animals produces alterations in neuronal activity in the ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus, ventral pallidum, anterior cingulate gyrus, septum and visual cortex as measured by blood oxygen level-dependent contrast (BOLD); 2) to determine how long nicotine sensitization persists; 3) to determine how the administration of monoamine oxidase inhibitors in conjunction with nicotine alters the persistence of sensitization; and 4) to investigate the role of glutamate in the expression of sensitization. This proposal is highly innovative in the use of fMRI to study sensitization. Once developed, this technique could be used to translate our knowledge of sensitization in animals to the study of sensitization in humans and its relation to addiction. The imaging of sensitization may provide a powerful new tool for the exploration of novel pharmacologic approaches to treating nicotine addiction, which is the largest contributor to preventable mortality in the developed world.

描述（由申请人提供）：大脑的功能磁共振成像（fMRI）提高了我们对滥用药物的理解。将这种方法应用于有意识的动物方面的进展很慢，因为在成像过程中，受试者必须不动。我们发明了一种设备，该设备使我们能够在醒着时对啮齿动物进行形象，从而为随着时间的流逝而开放了新的机会，可以随着时间的流逝研究大脑功能。反复接触滥用药物会引起运动刺激的逐渐增加，称为行为敏化。人们认为，敏化对包括尼古丁在内的药物成瘾至关重要。该重新提出解决了有关尼古丁致敏的两个潜在重要观察。首先，它可以用fMRI成像，从而识别涉及的大脑结构。可以通过在成像过程中施用选定的受体激动剂来评估单个神经递质在致敏化中的作用。我们的初步数据表明，fMRI可用于确定各个大脑区域对谷氨酸受体的敏化作用。该提议的目的是1）确定尼古丁对敏化动物的施用是否会导致腹侧段盖区域的神经元活性发生变化2）确定尼古丁的敏化持续时间； 3）确定单胺氧化酶抑制剂与尼古丁的施用如何改变敏化的持久性； 4）研究谷氨酸在敏化表达中的作用。该建议在使用fMRI来研究敏感性方面具有很高的创新性。一旦开发，该技术可用于将我们对动物的敏感性的了解转化为人类敏感性的研究及其与成瘾的关系。敏化的成像可能为探索新型药理方法来治疗尼古丁成瘾提供了一种强大的新工具，这是发达国家预防死亡率的最大贡献者。