权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Inhibitory Control and Drug Reward in Humans

人类的抑制控制和药物奖励

基本信息

批准号：
9042333
负责人：
HARRIET DE WIT
金额：
$ 19.55万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9042333
关键词：
Acute Address Adult Alcohols Animals Arousal Awareness Behavior Behavior Control Behavioral Characteristics Development Dextroamphetamine Drug Addiction Drug abuse Drug usage Drug user Euphoria Exhibits Foundations Goals Health Human Individual Investigation Laboratories Lead Link Measures Mediating Methamphetamine Mission Moods Neurobiology Participant Patient Self-Report Pharmaceutical Preparations Placebos Prevention Process Public Health Reporting Research Rewards Risk Risk Factors Signal Transduction Source Testing Therapeutic Agents Youth adverse outcome alcohol effect alcohol reward base behavior measurement behavioral response dopamine system drug abuse vulnerability drug of abuse drug reward experience improved innovation methamphetamine effect neurobiological mechanism novel preference prevent response targeted treatment young adult

项目摘要

DESCRIPTION (provided by applicant): Poor inhibitory control is a known risk factor for drug abuse. Individuals with poor inhibitory control may be at risk because they have difficulty refraining from actions (e.g., drug use) despite known adverse consequences. However, recent evidence suggests that these individuals may also be at risk for another reason: that they experience more positive subjective, or euphorigenic, effects from drugs. The long-term goal is to identify the mechanisms underlying risk for drug abuse in individuals with poor inhibitory control, and ultimately to develop therapeutic agents to reduce this risk. The objective here is to investigate associations between impulsive action (i.e., poor inhibitory control) and subjective and behavioral measures of the rewarding effects of methamphetamine and alcohol in healthy young adults. The central hypothesis is that individuals high in impulsive action will be more sensitive to the rewarding effects of both of these drugs. The rationale for this proposal is that behavioral evidence linking poor inhibitory control and drug reward sensitivity will lay the foundation for investigations of common neurobiological mechanisms underlying both risk factors. Such neurobiological mechanisms would serve as potential targets for therapeutic agents aimed at reducing risk for drug abuse in individuals with poor inhibitory control. The central hypothesis will be tested by addressing two specific aims: 1) examine the degree to which impulsive action in humans predicts stimulant drug reward and 2) examine the degree to which impulsive action predicts alcohol reward. For both aims, participants will be pre-selected as exhibiting low or high impulsive action, and then we will compare these groups' responses to the rewarding effects of the two drugs. Impulsive action, defined as difficulty controlling or inhibiting behavior, will be measured using the stop signal task, a well-validated measure of behavioral control. Under the first aim, the rewarding effects of methamphetamine (20 mg) will be compared in high and low impulsive individuals, using both subjective self-report measures of euphoria and arousal, and behavioral measures of drug choice. Under the second aim, a similar approach will be taken in separate groups of subjects, to examine the rewarding effects of alcohol (0.8 g/kg) in relation to baseline impulsive action. Based on preliminary findings with the prototypic stimulant d-amphetamine, it is hypothesized that individuals high in impulsive action will report significantly greater euphoria and arousal than those low in impulsive action following both methamphetamine and alcohol. Based on findings from animal studies, it is hypothesized that high impulsive individuals will also exhibit greater choice for both methamphetamine and alcohol over placebo. This approach is innovative because it examines a novel association between two risk factors for drug abuse, that have until now been studied separately. This contribution is significant because it is the first step to developing targeted therapy, both pharmacological and behavioral, to prevent and treat drug abuse in individuals with poor inhibitory control.

描述(由申请人提供)：不良的抑制控制是药物滥用的已知风险因素。抑制性控制不佳的个体可能面临风险，因为他们难以克制行动(例如，药物使用)，尽管已知的不良后果。然而，最近的证据表明，这些人也可能因为另一个原因而面临风险：他们从药物中体验到更多积极的主观或愉悦的影响。长期目标是确定抑制控制不良的个体药物滥用风险的潜在机制，并最终开发治疗药物来降低这种风险。这里的目标是在健康的年轻人中，调查冲动行为(即，不良的抑制控制)与甲基苯丙胺和酒精奖励效应的主观和行为测量之间的关系。中心假设是，冲动程度高的人会对这两种药物的回报效应更加敏感。这一建议的基本原理是，将不良的抑制控制与药物奖励敏感性联系起来的行为证据将为研究这两个风险因素背后的共同神经生物学机制奠定基础。这种神经生物学机制将成为治疗药物的潜在目标，旨在降低抑制控制不佳的个人的药物滥用风险。核心假设将通过解决两个具体目标来检验：1)检查人类冲动行为预测兴奋剂奖励的程度；2)检查冲动行为预测酒精奖励的程度。对于这两个目标，参与者将被预先选择为表现出低或高冲动行为，然后我们将比较这些组对两种药物的奖励效果的反应。冲动行为被定义为难以控制或抑制行为，将使用停止信号任务来衡量，这是一种经过充分验证的行为控制措施。在第一个目标下，将使用欣快感和觉醒的主观自我报告指标以及药物选择的行为指标来比较高冲动和低冲动个体服用甲基苯丙胺(20毫克)的回报效果。在第二个目标下，将在不同的受试组中采取类似的方法，检查酒精(0.8g/kg)相对于基线冲动行为的奖励效应。根据对典型兴奋剂d-苯丙胺的初步发现，假设冲动行为高的人在服用甲基苯丙胺和酒精后，会比冲动行为低的人报告更大的欣快感和唤醒。根据动物研究的发现，假设高冲动的人也会表现出比安慰剂更多的甲基苯丙胺和酒精的选择。这种方法是创新的，因为它检查了两个药物滥用风险因素之间的新联系，这两个因素到目前为止都是单独研究的。这一贡献意义重大，因为这是开发有针对性的药物治疗的第一步，包括药理学和行为学，以预防和治疗抑制控制不良的个人的药物滥用。