Gastrointestinal Core

项目摘要-胃肠道核心 胃肠核心将提供资源和创新专业知识来评估双向 药物滥用与胃肠道之间的相互作用和中枢作用。这其中的主要推动力是 新的核心源于对新化合物和药理学方法的评估的日益增长的需求 用于治疗无副作用的疼痛，尤其是与胃肠道有关的疼痛。近期 有证据表明肠道微生物群的改变影响中枢神经系统功能的几个方面，包括与 对于药物引起的焦虑和情绪，建议了解滥用药物对胃肠道的影响 很重要也很有必要。特别是，阿片类药物介导的胃肠功能障碍是一种主要影响。 这大大限制了它们在止痛方面的使用。此外，神经递质、受体和 肠道神经系统内的离子通道与中枢神经元中的离子通道相似，因此肠道也 为研究滥用药物的功能影响提供了一个有用的模型。最近的研究进一步表明 确定了肠道-脑轴是双向的，肠道生理的改变可以调节中枢 滥用药物的影响。GI核心的具体目标是：a)提供评估效果的资源 滥用药物对胃肠道功能的影响，包括体内和体外试验，以及b)评估滥用药物对胃肠功能的作用 微生物组对滥用药物的中枢/外周影响。我们还将利用我们最近开发的 从转基因小鼠和外源性感觉中分离和记录已鉴定的肠神经元的方法 从背根神经节的神经元，以评估滥用药物影响离子的机制 电导和决定微生物群在滥用药物的行为影响中的作用。超过了 在过去的十年里，VCU由NIDA资助的调查人员已经认识到有必要评估各种滥用药物 胃肠道。通过与阿克巴拉利实验室的合作，他们的研究得到了扩大 探讨内源性大麻素、Mu受体偏向配基、烟碱对阿片类药物的戒断作用 阿片类药物逆转便秘的激动剂及HIV-1Tat与吗啡在肠道内的相互作用 神经元，以及定义肠道微生物群在肠道疾病发育中的作用的假说。 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 与药物滥用有关的生理系统，并为药物滥用研究提供这一新兴领域的培训。

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.