Impulsivity and Demand for Drug in Rhesus Monkeys

恒河猴的冲动和对药物的需求

基本信息

批准号：
7751404
负责人：
GAIL D WINGER
金额：
$ 35.2万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-15 至 2013-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Two behavioral economic concepts have been described as related to human drug abuser: inability to delay gratification as indicated by a relatively high choice for small immediate reinforcers over delayed, larger reinforcers, and relatively inelasitc demand for the drug itself. Work in our laboratory with nonhuman primates has revealed that drugs with substantial abuse liability (e.g., cocaine or mu- opioid agonists) produce demand curves with less elasticity of demand than drugs with reduced abuse liability (e.g., ketamine or short-acting barbiturates). More recently, we have found marked individual differences among monkeys with respect to economic demand for various drugs of abuse. Furthermore monkeys that have a high demand for one drug are very likely to have high demand for all other tested drugs, suggesting that some monkeys may be more like human drug abusers, and other monkeys are more resistant to the reinforcing effects of drugs. We have begun to measure impulsivity in rhesus monkeys as well, using remifentanil, and to a lesser extent, food as the reinforcers. Evidence for an impulsivity trait is less clear than is the evidence for a "demand" trait. Nevertheless, there is a trend toward a significant correlation between high demand and high impulsivity in individual monkeys. In the present proposal, we propose to continue to investigate this possible relationship between a measure of drug abuse, and a measure of impulsivity. In addition, we propose to use monkeys that differ in their early-life rearing; specifically, the monkeys were raised either by their mothers, or in a nursery with peers of a similar age. Peer-rearing has been shown to result in an increased response to stressors and greater propensity to self-administer ethanol in previous studies, and we will determine if this correlates with impulsivity and/ or demand for drug. These experiments will help to evaluate the premise that impulsivity is trait that is genetically determined and/or established by a particular environment early in life. Understanding more about the cause-and-effect relation between drug abuse and impulsivity could assist in devising strategies for reducing impulsivity that could be adjuncts to drug treatment intervention and drug-use prevention programs. PUBLIC HEALTH RELEVANCE: This research is designed to evaluate in non-human primates whether impulsivity is a trait variable, whether it is influenced by early environment, and is related to vulnerability to drug abuse. This information will be useful in answering the question of whether impulsivity leads to drug abuse or drug abuse leads to impulsivity. This in turn will help clinicians and clinical investigators devise appropriate adjuncts to drug abuse intervention and treatment strategies based on modification of impulsive behavior.

描述（由申请人提供）：两个行为经济概念被描述为与人类滥用者有关的：无法延迟满足满足感，这是对小型立即加固者的选择，而不是延迟，较大的增强剂和对药物本身的相对较大的增强需求。我们的非人类灵长类动物的实验室工作表明，与具有降低滥用责任的药物相比，具有大量滥用责任的药物（例如，可卡因或混血动力学家）产生的需求曲线较小（例如氯胺酮或短效应型巴比妥酸盐）。最近，我们发现猴子在对各种滥用药物的经济需求方面有明显的个体差异。此外，对一种药物的需求很高的猴子很可能对所有其他测试药物都有很高的需求，这表明某些猴子可能更像人类的滥用药物，而其他猴子则对药物的增强作用更具抵抗力。我们也开始使用瑞芬太尼（Rebifentanil）以及较小程度地衡量恒河猴的冲动性，就像增强剂一样。冲动性状的证据不及“需求”特征的证据。然而，单个猴子的高需求和高冲动性之间存在显着相关性的趋势。在本提案中，我们建议继续研究药物滥用量与冲动度量之间的这种可能的关系。此外，我们建议使用在早期养育中不同的猴子。具体而言，猴子是由母亲或与同龄人相似的托儿所抚养的。在以前的研究中，培养同伴的培养会导致对压力源的反应增加，并且对自助乙醇的倾向更大，我们将确定这是否与冲动性和/或对药物的需求有关。这些实验将有助于评估冲动性是在生命早期特定环境确定和/或建立的遗传性特征的前提。更多地了解药物滥用和冲动之间的因果关系，可以帮助制定策略，以减少冲动性，这可能是药物治疗干预和药物使用预防计划的辅助手段。公共卫生相关性：这项研究旨在在非人类灵长类动物中评估冲动性是否为特质变量，是否受到早期环境的影响，并且与易受药物滥用的脆弱性有关。这些信息将在回答冲动性是否导致药物滥用或吸毒导致冲动的问题上很有用。反过来，这将帮助临床医生和临床研究人员根据脉冲行为的修改为药物滥用干预和治疗策略设计适当的辅助手段。