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: 7380000
• 负责人: William L. Woolverton
• 金额: $ 31.28万
• 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/7380000
• 关键词: Agonist; Animal Model; Barbiturates; Basic Science; Behavioral; Central Nervous System Depressants; Class; Cocaine; Collection; Complex; Data; 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; improved; multidrug abuse; neurobehavioral; nonhuman primate; pre-clinical; programs; receptor; research study; response; therapy development

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.

多种药物滥用是一个严重的公共卫生问题在美国和其他地方，尽管我们的理解