Nature and Predictors of Impaired Harm Avoidance in Polysubstance Abuse

项目概要/摘要 阿片类药物过量，作为阿片类单一物质使用 (MSU) 的一部分而发生，更严重的是，其中 多物质使用（PSU），已在美国达到流行水平，并反映了其他 PSU 患者中的高风险行为。因此，迫切需要改善公共卫生 以病因学和性质的发现为指导，针对这些人群制定治疗和预防策略 实验室评估和临床避免伤害缺陷。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）可能是毁灭性的、临床避免伤害缺陷的基础，其特征是高 与阿片类药物 PSU 患者相比，血源性病毒、犯罪和反复服用过量的风险 密歇根州立大学。在动物模型中，我们检查实验室评估的伤害避免缺陷是否存在（通过评估） 药物自我管理惩罚和随后的操作性回避范式）源于预先存在的 抑制控制缺陷、药物使用或这些因素的组合，特别评估 单一（海洛因或可卡因）与多聚（海洛因可卡因）物质使用模型中的避免伤害能力。我们的 后续在人类中的工作将使用两种基于恐惧的方法（获得习得性恐惧关联、操作性回避） 该协会）和两项基于货币的（爱荷华州赌博任务和货币选择）实验室措施 的伤害避免缺陷，以比较门诊患者和实验室患者的实验室伤害避免缺陷的严重程度 阿片类药物 MSU 或阿片类兴奋剂 PSU。我们将使用这些措施来预测和了解 该男性和女性样本中存在临床避免伤害缺陷。已经建立了紧密的模拟程序 进入动物和人类研究，人类研究提供了准实验或联想 动物范式的复制，即允许严格控制的实验证据（允许因果关系） 结论），以帮助设计和解释较少控制的预测模型 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.