Inhibitory Control and Drug Reward in Humans

人类的抑制控制和药物奖励

• 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
• 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

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（由申请方提供）：不良抑制控制是药物滥用的已知风险因素。抑制控制能力差的人可能有风险，因为他们很难克制自己的行为（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处于危险之中：他们从药物中体验到更积极的主观或欣快的效果。长期目标是确定抑制控制不良的个体中药物滥用风险的潜在机制，并最终开发治疗药物以降低这种风险。我们的目标是 调查冲动行为（即，不良的抑制控制）以及甲基苯丙胺和酒精对健康年轻人的奖励作用的主观和行为测量。核心假设是，冲动行为高的个体对这两种药物的奖励效果更敏感。这一建议的理由是，行为证据联系不良的抑制控制和药物奖励敏感性将奠定基础的共同神经生物学机制的调查这两个危险因素。这种神经生物学机制将作为治疗药物的潜在靶点，旨在降低抑制控制不良个体的药物滥用风险。中心假设将通过解决两个具体目标进行测试：1）检查人类冲动行为预测兴奋剂药物奖励的程度，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群体对两种药物的奖励效果的反应。冲动行为，定义为难以控制或抑制行为，将使用停止信号任务进行测量，这是一种经过充分验证的行为控制措施。根据第一个目标，甲基苯丙胺（20毫克）的奖励效果将比较高和低冲动的个人，使用主观自我报告的欣快和觉醒的措施，和药物选择的行为措施。在第二个目标下，将在不同的受试者组中采用类似的方法，以检查与基线冲动行为相关的酒精（0.8 g/kg）的奖励效应。根据原型兴奋剂d-苯丙胺的初步研究结果，假设在甲基苯丙胺和酒精之后，冲动行为高的个体会比冲动行为低的个体报告显着更大的欣快感和觉醒。根据动物研究的结果，假设高冲动的个体也会表现出对甲基苯丙胺和酒精的选择多于安慰剂。这种方法是创新的，因为它研究了两种药物滥用风险因素之间的新关联，到目前为止，这两种风险因素一直被单独研究。这一贡献是重要的，因为它是第一步，以发展有针对性的治疗，药理学和行为，以预防和治疗药物滥用的个人与穷人的抑制控制。