Gastrointestinal Core

胃肠核心

• 批准号: 10374826
• 负责人: HAMID I AKBARALI
• 金额: $ 25.03万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374826
• 关键词: Affect; Afferent Neurons; Anxiety; Awareness; Bacterial Translocation; Bathing; Behavioral; Biological Assay; Chronic; Cocaine; Collaborations; Colon; Complement; Constipation; Development; Drug Evaluation; Drug abuse; Drug usage; Dyes; Endocannabinoids; Enteral; Enteric Nervous System; Epithelial; Evaluation; Functional disorder; Funding; Gastrointestinal Motility; Gastrointestinal Physiology; Gastrointestinal Transit; Gastrointestinal tract structure; Goals; Gram-Positive Bacteria; HIV-1; In Vitro; Ion Channel; Laboratories; Ligands; Mediating; Methodology; Modeling; Moods; Morphine; Mus; Muscle; Myenteric Plexus; National Institute of Drug Abuse; Neuraxis; Neurons; Neurotransmitter Receptor; Nicotinic Agonists; Opioid; Oral; Organ; Oxycodone; Pain; Peripheral; Pharmaceutical Preparations; Pharmacology; Physiological; Physiology; Research; Research Personnel; Resources; Role; Scientist; Spinal Ganglia; System; Techniques; Training; Transgenic Mice; United States National Institutes of Health; Vancomycin; Virginia; cytokine; drug of abuse; gastrointestinal; gastrointestinal epithelium; gastrointestinal function; gut bacteria; gut microbiome; gut-brain axis; ileum; in vitro Assay; in vivo; innovation; microbiome; microbiome alteration; mu receptors; opiate tolerance; opioid sparing; pain relief; patch clamp; prevent; ranpirnase; side effect; stem

Project Summary – Gastrointestinal Core The Gastrointestinal Core will provide the resources and innovative expertise to evaluate the bi-directional interaction between the gastrointestinal tract and central effects of drugs of abuse. The major impetus for this new core stems from the growing need for the evaluation of new compounds and pharmacological approaches to treat pain that are devoid of side-effects, particularly those associated with the gastrointestinal tract. Recent evidence that alterations in the gut microbiome affects several aspects of CNS functions, including those related to drug-induced anxiety and mood, suggests that understanding gastrointestinal effects for drugs of abuse is important and necessary. In particular, opioid-mediated gastrointestinal dysfunction represents a major effect that significantly limits their use for pain relief. Additionally, the complement of neurotransmitters, receptors and ion channels within the enteric nervous system are similar to those in the central neurons, and thus the gut also provides a useful model to examine the functional effects of drugs of abuse. Recent studies have further established that the gut-brain axis is bidirectional in which alterations of gut physiology can modulate central effects of drugs of abuse. The specific aims of the GI Core are to a) provide the resources to evaluate the effects of drugs of abuse on GI function, including in vivo and in vitro assays, and b) to evaluate the role of the microbiome on the central/peripheral effects of drugs of abuse. We will also utilize our recently developed methodologies to isolate and record from identified enteric neurons from transgenic mice and extrinsic sensory neurons from the dorsal root ganglia, to evaluate the mechanisms by which drugs of abuse affect ionic conductances and determine the role of the microbiome in the behavioral effects of drugs of abuse. Over the last decade, NIDA-funded investigators at VCU have recognized the need to evaluate various drugs of abuse in the gastrointestinal tract. Through collaboration with the Akbarali laboratory, their research has been expanded to investigate opioid sparing effects of endocannabinoids, mu receptor biased ligands, the effects of nicotinic agonists in reversal of opioid-induced constipation, and the interaction of HIV-1 Tat and morphine in enteric neurons, as well as developed the hypothesis defining the role of the gut microbiome in the development of opioid tolerance. Thus, this core enables young and established investigators to delve into an important physiological system relevant to drug abuse and provides training in this emerging field for drug abuse research.

项目总结-胃肠道核心 胃肠核心将提供资源和创新的专业知识，以评估双向 滥用药物的胃肠道和中枢效应之间的相互作用。主要的推动力是 新的核心源于对新化合物和药理学方法评估的日益增长的需求 以治疗没有副作用的疼痛，特别是与胃肠道相关的疼痛。最近 有证据表明，肠道微生物组的改变会影响CNS功能的几个方面，包括那些相关的 药物引起的焦虑和情绪，表明了解滥用药物对胃肠道的影响， 重要和必要的。特别是阿片类药物介导的胃肠道功能障碍是一个主要的影响， 这极大地限制了它们用于缓解疼痛的用途。此外，神经递质、受体和 肠神经系统内的离子通道类似于中枢神经元中的离子通道，因此肠也 提供了一个有用的模型来检查滥用药物的功能影响。最近的研究进一步 建立了肠-脑轴是双向的，其中肠道生理学的改变可以调节中枢神经系统。 滥用药物的影响。全球影响力核心的具体目标是：a）提供资源以评估影响 包括体内和体外试验，和B）评估药物滥用对GI功能的作用， 微生物组对滥用药物的中枢/外周效应的影响。我们还将利用我们最近开发的 从来自转基因小鼠和外源性感觉神经元的鉴定的肠神经元分离和记录的方法 神经元的背根神经节，以评估滥用药物影响离子 电导和确定微生物组在药物滥用行为影响中的作用。来 在过去的十年中，NIDA资助的VCU研究人员已经认识到有必要评估各种滥用药物， 胃肠道通过与Akbarali实验室的合作，他们的研究得到了扩展 为了研究内源性大麻素、μ受体偏向性配体的阿片样物质节省作用， 逆转阿片类药物诱导的便秘的激动剂，以及HIV-1达特和吗啡在肠道中的相互作用 神经元，以及发展的假设定义的作用，肠道微生物组的发展， 阿片耐受性因此，这个核心使年轻和成熟的调查人员能够深入研究一个重要的 生理系统有关的药物滥用，并提供培训，在这一新兴领域的药物滥用研究。