Vulnerability to the Reinforcing Effects of Opioids

易受阿片类药物增强作用的影响

• 批准号: 6318960
• 负责人: DRAKE MORGAN
• 金额: $ 9.89万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6318960
• 关键词: autoradiography; biological signal transduction; disease /disorder proneness /risk; drug addiction; heroin; laboratory rat; male; opioid receptor; receptor coupling; reinforcer

DESCRIPTION: (provided by applicant) Current estimates suggest that there are 600,000 people in need of treatment for heroin addiction. Unfortunately, there is very little scientific data regarding vulnerability to heroin abuse. This makes it extraordinarily difficult to study the biological substrates responsible for the findings that some people exposed to heroin progress to a compulsive and uncontrolled use of the drug, whereas others use heroin several times, and then stop using it. This question is impossible to experimentally evaluate in humans because of the obvious ethical issues involved in exposing drug-naive people to heroin. If animal models are to be used to understand this phenomenon, then appropriate self-administration methods that allow for a differential sensitivity to be expressed need to be developed. Furthermore, if a procedure that screens for this eventual "vulnerability" was used, then biological studies can be conducted in essentially drug-naive animals, allowing the determination of the mechanisms that produce this differential reaction to drugs of abuse. This proposal is designed to investigate the relationship between sensitivity to the analgesic effects of opioids and various measures of the reinforcing effects of opioids (primarily heroin). Once this relationship is established, animals can be screened for "vulnerability" to drug addiction, and extensive neurobiological and biochemical analyses can be conducted in drug-naive animals. In particular, the following questions will be answered over the course of this award: 1. What is the relationship between sensitivity to the analgesic effects and the reinforcing effects of opioids? 2. What are the differences in the localization, characteristics, or coupling efficiency of the opioid system across subgroups (i.e. "vulnerable" or "resistant") of animals? 3. What are the differences in the expression of various genetic markers and proteins in the brain pathways relevant to opioid reinforcement across these subgroups of animals? This series of experiments will provide extensive training for the candidate in the neurobiology and biochemistry of drug abuse, to complement the behavioral background already established. In the end, this research will identify neurobiological, biochemical and genetic determinants of susceptibility to heroin use. An improved understanding of the individual risk of drug addiction will lead to the development of better prevention and treatment strategies.

描述：（申请人提供） 目前的估计表明，有60万人需要治疗 海洛因成瘾。不幸的是，科学数据很少 关于滥用海洛因的脆弱性。这使它非常 难以研究负责发现的生物基质 有些人暴露于海洛因的进展 该药物，而其他人则多次使用海洛因，然后停止使用它。这 问题是不可能在人类中进行实验评估的 暴露毒品的人涉及海洛因的明显道德问题。如果 动物模型应用于理解这种现象，然后适当 允许差异灵敏度的自我管理方法 表示需要开发。此外，如果一个程序屏幕 使用了最终的“脆弱性”，那么生物学研究可以是 在本质上是毒品的动物中进行的，允许确定 对滥用药物产生这种不同反应的机制。这 建议旨在调查敏感性与 阿片类药物的镇痛作用和各种措施的增强作用 阿片类药物（主要是海洛因）。一旦建立了这种关系，动物就可以 被筛选为吸毒成瘾的“脆弱性”和广泛的 可以在药物中进行神经生物学和生化分析 动物。特别是，以下问题将在 本奖项的课程： 1。敏感性对镇痛作用的敏感性与 阿片类药物的增强作用？ 2。在本地化，特征或耦合方面有什么区别 跨亚组的阿片类药物系统的效率（即“脆弱”或 动物的“抗药性”？ 3。各种遗传标记的表达和 大脑途径中的蛋白质与阿片类药物增强有关 动物亚组？ 这一系列实验将为候选人提供广泛的培训 药物滥用的神经生物学和生物化学，以补充行为 背景已经建立。最后，这项研究将确定 易感性的神经生物学，生化和遗传决定因素 海洛因使用。对吸毒成瘾的个人风险有了改进的了解 将导致发展更好的预防和治疗策略。