Patterns and neurocognitive consequences of opioid-alcohol polysubstance use

阿片类酒精多物质使用的模式和神经认知后果

• 批准号: 10659347
• 负责人: Linda B. Cottler
• 金额: $ 44.78万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659347
• 关键词: Acute; Address; Adopted; Adverse effects; Affect; Alcohol consumption; Alcohols; Animal Model; Back; Base Sequence; Behavior; Behavioral; Biological; Cognition; Cognitive; Cognitive deficits; Consumption; DSM-V; Data; Decision Making; Diagnosis; Disease; Drug Kinetics; Drug usage; Episodic memory; Focus Groups; Frequencies; Goals; Health; Hour; Human; Impaired cognition; Impairment; Impulsivity; Individual; Intake; Interview; Knowledge; Long-Term Effects; Longitudinal Studies; Modeling; Motivation; Neurobiology; Neurocognitive; Opioid; Oral Administration; Outcome; Oxycodone; Participant; Pathologic; Patient Recruitments; Pattern; Pharmaceutical Preparations; Phase; Positioning Attribute; Pre-Clinical Model; Publishing; Rattus; Relapse; Reporting; Research; Research Design; Rodent; Rodent Model; Role; Self Administration; Sequence Analysis; Severities; Short-Term Memory; Substance abuse problem; Testing; Therapeutic; Time; Translating; Treatment outcome; Typology; Withdrawal; adverse outcome; alcohol comorbidity; alcohol involvement; biobehavior; clinically relevant; cognitive function; community engagement; drug metabolism; flexibility; follow-up; human data; interest; meetings; multidisciplinary; neural circuit; neuroadaptation; neurobehavioral; novel; opioid injection; opioid overdose; opioid use; opioid use disorder; opioid user; phase 2 study; polysubstance abuse; polysubstance use; programs; response; substance use; therapy development; trend

Project Abstract Opioid-alcohol polysubstance use (PSU) is a clinically-relevant problem, as it worsens the trajectories and outcomes of opioid use disorder (e.g., 14-16% of opioid overdoses also involve alcohol). Both alcohol and opioid use alone are associated with significant neurobehavioral consequences, such as impaired cognition, but it is not currently known if there are additive or synergistic impairments in such domains in opioid-alcohol PSU. In order to determine the mechanisms underlying the deleterious consequences of opioid-alcohol PSU (e.g. motivation to seek drug, relapse, cognition), rodent models are necessary. Here, we propose to develop novel rodent models based on back-translated data from human opioid-alcohol polysubstance users. Thus, in this 2- phase R61/R33 proposal, we will first assess human temporal patterns of opioid and alcohol use, in terms of hour-by-hour and day-by-day use, using our novel assessment, the PolySubstance Use – Temporal Pattern Section (PSU-TPS). We will also use the Substance Abuse Module-5 (SAM-5) to determine quantity, frequency, and duration (QFD) of use and the presence of use disorders. These data will be used to define clusters of PSU patterns, based on hours/day and days/month of use, and whether use is sequential, concurrent, or simultaneous. In the same participants, cognition will be assessed at baseline and one year later. The domains of interest include working and episodic memory, impulsivity, risky decision-making, and cognitive flexibility. We will determine associations between opioid/alcohol use and cognition at both baseline and at the one year follow- up. We will also compare the adverse consequences of use between PSU clusters, with a focus on QFD of use, percent meeting DSM-V criteria for use disorder, and cognitive impairments. We will then back-translate the most prevalent PSU patterns with deleterious consequences into rodents for the assessment of intravenous opioid self-administration, motivation to seek opioids using demand curve analyses, and relapse to opioid- seeking. We will also use rodent models to directly test the role of opioid and alcohol use and polysubstance use on such cognitive impairments, using rodent tasks that have been established to assess the same domains as in humans. We will also assess whether the two patterns of PSU alter the pharmacokinetics of alcohol and opioids. This proposed 2-phase study brings together a multidisciplinary team of experts in their fields to conduct novel assessments of the patterns and consequences of real-world opioid-alcohol polysubstance use for the establishment of translational animal models that can advance the field.

项目摘要 阿片类酒精饮料多物质使用（PSU）是一个与临床相关的问题，因为它使轨迹和轨迹恶化 蛋白质使用障碍的结局（例如，14-16％的卵毒素过量剂量也涉及酒精）。酒精和绿o 单独使用与明显的神经行为后果有关，例如认知受损，但这是 目前尚不清楚阿片类药物PSU中此类域中是否存在加性或协同损害。在 为了确定阿片类酒精PSU所删除后果的基础机制（例如 寻求药物，救济，认知的动机），啮齿动物模型是必要的。在这里，我们建议开发小说 啮齿动物模型基于来自人类阿片类酒精饮料的用户的反翻译数据。那，在这个2- R61/R33阶段提案，我们将首先评估阿片类药物和酒精使用的临时临时模式 每小时和日常使用，使用我们的新颖评估，Polysubstance使用 - 时间模式 部分（PSU-TPS）。我们还将使用药物滥用模块-5（SAM-5）来确定数量，频率， 和使用持续时间（QFD）和使用障碍的存在。这些数据将用于定义PSU的簇 基于使用时间/天/天/月的模式，以及使用是顺序，并发还是 简单的。在同一参与者中，认知将在基线和一年后进行评估。域 感兴趣的包括工作和情节记忆，冲动，风险的决策和认知灵活性。我们 将确定基线和后续一年的阿片类药物/酒精使用与认知之间的关联 - 向上。我们还将比较PSU簇之间使用的不利后果，重点是使用QFD， 符合使用障碍和认知障碍的DSM-V标准的百分比。然后，我们将对此进行反翻译 大多数普遍的PSU模式具有有害后果，以评估静脉 卵巢自我给药，使用需求曲线分析寻求绿o的动机，并继电器 - 寻求。我们还将使用啮齿动物模型直接测试阿片类药物和酒精使用和多核酸的作用 在这种认知障碍上，使用已建立的啮齿动物任务来评估与 在人类中。我们还将评估PSU的两种模式是否改变了酒精的药代动力学和 阿片类药物。这项提出的2阶段研究汇集了一个多学科的专家团队，以进行行为 对现实世界中阿片类药物多饮料的模式和后果的新颖评估 建立可以推进该领域的翻译动物模型。