The Microbiome in opioid use and abuse

阿片类药物使用和滥用中的微生物组

基本信息

批准号：
10403903
负责人：
CHERYL ALLYNE WHISTLER
金额：
$ 8.91万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10403903
关键词：
Absence of pain sensation Abstinence Acute Acute Pain Animal Behavior Animals Antibiotics Anxiety Attention Behavior Behavioral Brain Central Nervous System Diseases Collaborations Complex Data Dependence Diagnostic Disease Dose Drug Exposure Drug usage Environmental Risk Factor Exhibits Extinction (Psychology)Family Funding Generations Genes Genetic Goals Health Human Impulsivity Inbreeding Individual Intestines Lead Life Style Link Longitudinal Studies Mental Depression Mental disorders Metabolic Diseases Metagenomics Microbiology Molecular Morphine Mus National Institute of Drug Abuse Neurodegenerative Disorders Opioid Opioid Analgesics Opioid Receptor Opioid abuser Oral Outcome Overdose Pain Parkinson Disease Pathogenicity Patients Pharmaceutical Preparations Pharmacology Postoperative Pain Principal Investigator Race Relapse Reporting Rewards Risk Risk Factors Rodent Role Schizophrenia Science Self Administration Sister Therapeutic Touch sensation United States Variant Work addiction autism spectrum disorder behavioral outcome chronic pain chronic painful condition design drug abuser drug seeking behavior gut microbiome gut-brain axis high risk host-microbe interactions interest microbial microbiome microbiome composition microbiome signature mouse model nervous system disorder opioid abuse opioid epidemic opioid overdose opioid overuse opioid use pain patient pain relief preference prescription opioid response skills statistics stem tool trend

项目摘要

Summary Currently we are faced with a significant conundrum with regard to the opioid crises. On the one hand, we have no viable alternative for treating severe post-surgical and chronic pain. On the other hand, people taking these drugs for legitimate purposes are transitioning at an alarming rate to opioid overuse and abuse. While the dramatic increase in opioid abuse has coincided with the much-reported increase in opioid prescriptions, it is still true that only a fraction of patients who are prescribed opioids for pain transition to abuse. If we could identify those pain patients most at risk prior to opioid treatment, we could potentially stem the tide of opioid abuse. A number of compelling studies have recently shown that alterations in the gut microbiome can influence a plethora of central nervous systems disorders, leading to widespread acceptance of the concept of a gut-microbiome- brain axis. We find it compelling that, coincident with the increase in opioid prescriptions, there has also been a large increase in the routine and often unnecessary use of oral antibiotics—a trend that that has altered the gut microbiome of an entire generation. Not surprisingly, given the widespread expression of opioid receptors in the gut, opioids have been shown to alter the gut microbiome. Furthermore, alterations in the microbiome have been shown to alter opioid analgesia and reward, suggesting that opioids influence the gut-brain axis. However, to date, no studies have examined whether the gut microbiome influences abuse liability. Here we will capitalize on both behavioral variability in a mouse model of compulsive drug seeking and relapse, and mouse microbiome variability, both innate and in response to morphine, to determine whether abuse liability and the microbiome co- vary (Aim 1). We will also examine whether the microbiome from an “addict” mouse or “non-addict” mouse can predispose to or protect subjects from compulsive drug seeking or relapse (Aim 2). This project is a dual Principal Investigator proposal that capitalizes on the complementary expertise of two experts in their respective fields, one a molecular microbiologist the other an opioid pharmacologist.

概括目前，我们面临着阿片类药物危机的重大难题。没有可行的替代方法来治疗严重的术后疼痛和慢性疼痛，另一方面，人们服用这些药物。出于合法目的，正在以惊人的速度将药物转变为阿片类药物的过度使用和滥用。阿片类药物滥用的急剧增加与阿片类药物处方的增加同时发生，但仍确实，如果我们能确定的话，只有一小部分服用阿片类药物治疗疼痛的患者会转向滥用。对于那些在接受阿片类药物治疗之前风险最高的疼痛患者，我们有可能阻止阿片类药物滥用的浪潮。最近许多令人信服的研究表明，肠道微生物组的改变可以影响很多方面中枢神经系统疾病，导致肠道微生物组概念被广泛接受我们发现令人信服的是，随着阿片类药物处方的增加，也出现了口服抗生素的常规使用和经常不必要的使用大量增加——这一趋势已经引起了人们的注意鉴于阿片受体在人类中的广泛表达，这一点并不奇怪。肠道，阿片类药物已被证明可以改变肠道微生物组此外，微生物组也发生了改变。研究显示，阿片类药物可以改变镇痛和奖赏，这表明阿片类药物会影响肠-脑轴。迄今为止，还没有研究检验肠道微生物组是否影响滥用倾向。关于强迫性药物寻求和复发的小鼠模型的行为变异性以及小鼠微生物组固有的和对吗啡的反应的变异性，以确定滥用倾向和微生物组是否共同变化（目标 1）。我们还将检查来自“成瘾”小鼠或“非成瘾”小鼠的微生物组是否可以。预防或保护受试者免受强迫性药物寻求或复发（目标 2）。研究者的建议利用了两位专家在各自领域的互补专业知识，一位是分子微生物学家，另一位是阿片类药理学家。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Deletion of arrestin-3 does not improve compulsive drug-seeking behavior in a longitudinal paradigm of oral morphine self-administration.

在口服吗啡自我给药的纵向范式中，删除抑制蛋白-3并不能改善强迫性寻药行为。

DOI：
发表时间：
2024-03-22
期刊：
影响因子：
0
作者：
Gooding, Sarah Warren;Felth, Lindsey;Foxall, Randi;Rosa, Zachary;Ireton, Kyle;Sall, Izabella;Gipoor, Joshua;Gaur, Anirudh;King, Madeline;Dirks, Noah;Whistler, Cheryl A;Whistler, Jennifer L
通讯作者：
Whistler, Jennifer L

A Balancing Act: Learning from the Past to Build a Future-Focused Opioid Strategy.

平衡之举：汲取过去的教训，制定面向未来的阿片类药物战略。