Self-administration of drug combinations: Polydrug abuse

药物组合的自我给药：多种药物滥用

• 批准号: 7577494
• 负责人: William L. Woolverton
• 金额: $ 31.27万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7577494
• 关键词: Agonist; Animal Model; Barbiturates; Basic Science; Behavioral; Central Nervous System Depressants; Cocaine; Collection; Complex; Data Collection; Detection; Development; Dose; Drug Combinations; Drug Interactions; Drug Kinetics; Drug abuse; Foundations; Government; Human; Laboratories; Laboratory Research; Ligands; Modeling; Nature; Neurobiology; Opioid; Pharmaceutical Preparations; Public Health; Research; Research Personnel; Self Administration; Staging; Techniques; Testing; Time; barbituric acid salt; design; dopamine transporter; drug of abuse; epidemiologic data; improved; multidrug abuse; neurobehavioral; nonhuman primate; pre-clinical; programs; receptor; research study; response; therapy development; treatment strategy

Polydrug abuse is a serious public health problem in the US and elsewhere, though our understanding of the mechanisms controlling polydrug abuse is limited. Laboratory research can help establish more precisely these mechanisms and, thereby, contribute to rational approaches to the development of interventions. The research outlined in this proposal will use a laboratory model, drug self-administration by non-human primates, and current pharmacological approaches to understanding drug interactions, to study the self- administration of drag combinations. More particularly, we will test the overarching hypothesis that super- addictive reinforcing effects contribute to the abuse of the most problematic drag-combinations. To test this hypothesis, we will first study drag combinations selected to provide basic information about self-administration of combinations and to establish our analytical approach. Specific Aim 1 is to study the reinforcing effects of combinations of drags with comparable mechanisms of action. Two stimulants (dopamine transporter ligands) will be studied alone and in combination, as will two opioids (ji receptor agonists) and two depressants (barbiturates). We hypothesize that drags within a pharmacological class will be additive in terms of reinforcing effects. Specific Aim 2 is to examine combinations of drags across pharmacological class, i.e., with different mechanisms of action. Stimulant-opioid, stimulant-depressant and opioid-depressant combinations will be studied. We hypothesize that across pharmacological class (e.g., stimulant/opioid) these combinations will be non-additive in terms of reinforcing effects. Specific Aim 3 is to examine commonly abused combinations of cocaine with other drags. The hypothesis of this aim is that the combinations that are most problematic in humans are super-additive in their reinforcing effects. The studies in this proposal are designed with the aim of developing a framework for establishing a broadly applicable animal model of polydrag abuse. In this respect, our model should facilitate understanding neurobehavioral underpinnings of the reinforcing effects of drag combinations. Moreover, our model should provide key information for the development of improved strategies for the treatment of polydrag abuse.

滥用多药是美国和其他地方的严重公共卫生问题，尽管我们对 控制滥用多药的机制是有限的。实验室研究可以帮助建立更精确的 这些机制，从而有助于理性的干预措施。 该提案中概述的研究将使用实验室模型，非人类的药物自我管理 灵长类动物以及当前了解药物相互作用的药理方法，以研究自我 阻力组合的给药。更特别地，我们将测试超级假设 上瘾的增强作用有助于滥用最有问题的拖曳组合。 为了检验这一假设，我们将首先选择选定的阻力组合来提供有关的基本信息 组合的自我管理并建立我们的分析方法。具体目标1是研究 加强阻力组合与可比的作用机理的影响。两个兴奋剂 （多巴胺转运蛋白配体）将单独研究，并组合使用，两种阿片类药物也会进行研究（JI受体 激动剂）和两种抑郁剂（巴比妥酸盐）。我们假设在药理学类中拖动将 在增强效果方面是加性的。特定目的2是检查横跨阻力的组合 药理学类别，即具有不同的作用机理。刺激性阿片类药物，刺激性抑制剂和 将研究阿片类抑制剂的组合。我们假设整个药理学类别（例如 刺激剂/阿片类药物）这些组合在增强作用方面将是非加性的。具体目标3是 检查通常滥用可卡因与其他阻力的组合。这个目标的假设是 在人类中最有问题的组合在增强作用方面是超级添加的。 该提案中的研究旨在开发一个框架来建立一个 广泛适用的滥用多重动物模型。在这方面，我们的模型应促进理解 阻力组合增强作用的神经行为基础。而且，我们的模型应该 提供关键信息，以制定改进的策略来治疗滥用多龙虾。