Nature and Predictors of Impaired Harm Avoidance in Polysubstance Abuse

项目总结/摘要 阿片类药物过量，作为阿片类单一物质使用（MSU）的一部分发生，更严重的是， 与多物质使用（PSU），已达到流行病的水平，在美国，并反映了其他 PSU患者的高危行为。因此，迫切需要改善公共卫生， 这些人群的治疗和预防战略，以病因学和性质的发现为指导， 实验室评估和临床避免伤害的缺陷。我们的目的是评估性质和 实验室评估的伤害避免缺陷的重要性，以确定潜在的治疗目标 （机械结果），可能是破坏性的，临床伤害避免缺陷的基础，其特征是高 与阿片类PSU患者相比， 密歇根州立大学。在动物模型中，我们研究了实验室评估的伤害回避缺陷（通过 药物自我管理惩罚和随后的操作性回避范例）产生于预先存在的 抑制性控制缺陷、药物使用或这些因素的组合，特别是评估 单一（海洛因或可卡因）与多（海洛因+可卡因）物质使用模型中的避免伤害能力。我们 随后的人类研究将使用两种基于恐惧的方法（习得恐惧联想、操作性回避 和两个基于货币的实验室测量（爱荷华州赌博任务和货币选择 的伤害避免缺陷，比较门诊患者的实验室伤害避免缺陷的严重程度， 阿片类MSU或阿片类+兴奋剂PSU。我们将使用这些措施来预测和理解的性质， 在这个男性和女性样本中的临床伤害回避缺陷。已经建立了密切的模拟程序 动物和人类研究，人类研究提供了一个准实验或联想 动物范例的复制，即，允许严格控制的实验证据（允许因果关系） 结论），以帮助设计和解释控制较少的预测模型， 人类阶段。

PROJECT SUMMARY/ABSTRACT Opioid overdose, occurring as part of opioid mono-substance use (MSU) and, more intensely, among those with poly-substance use (PSU), has reached an epidemic level in the United States, and is reflective of other high-risk behaviors among those with PSU. Accordingly, there is an urgent public health need for improved treatment and prevention strategies for these populations, as guided by findings on the etiology and nature of both laboratory-assessed and clinical harm-avoidance deficits. Our purpose is to evaluate the nature and significance of laboratory-assessed harm avoidance deficits in order to identify potential treatment targets (mechanistic outcomes) that may underlie devastating, clinical harm-avoidance deficits, characterized by high risk for blood-borne viruses, criminality, and repeated overdoses among those with opioid PSU relative to MSU. In the animal model, we examine whether laboratory-assessed harm avoidance deficits (assessed via drug self-administration punishment and subsequent operant avoidance paradigms) arise from pre-existing inhibitory control deficits, drug use, or the combination of these factors, specifically evaluating differences in harm-avoidance capacity in mono (heroin or cocaine) vs. poly (heroin + cocaine) substance use models. Our subsequent work in humans will use two fear-based (acquisition of learned fear association, operant avoidance of this association) and two monetary-based (Iowa Gambling Task and monetary choice) laboratory measures of harm avoidance deficits to compare the severity of laboratory harm avoidance deficits in outpatients with opioid MSU or opioid+stimulant PSU. We will use these measures to predict and understand the nature of clinical harm-avoidance deficits in this sample of men and women. Close analogue procedures have been built into the animal and human studies, with the human studies providing a quasi-experimental or associative replication of the animal paradigms, i.e., allowing the tightly controlled experimental evidence (allowing causal conclusions) from the animal phase to aid the design and interpretation of less controlled, predictive models in the human stage.