INHIBITORY CONTROL AND MA SELF-ADMINISTRATION MODAFINIL EFFECTS

项目2的总体目标是在基础研究项目之间建立联系， 机械的见解和临床研究的协调计划。我们建议评估协会 抑制控制功能（反应抑制）是一种行为功能， 在成瘾中的重要作用，以及实验室中MA依赖性人类志愿者的MA自我给药 设置.我们将通过评估莫达非尼的作用来实现这一目标，莫达非尼是一种已知的增强 使用MA自我给药的人类实验室模型对MA自我给药的抑制控制功能。 目标1.确定莫达非尼治疗对人自身MA给药的影响 MA自我管理的实验室模型。 在项目1活动（反应抑制及其神经生物学研究）完成后， 在MA依赖和对照受试者中相关），MA依赖参与者将进入项目2。时程 将评估莫达非尼或安慰剂预处理后MA的主观效应 使用自我报告评级量表（“高”，“渴望MA”等）因为药物的主观影响经常 与其强化效果平行。将检测MA的强化作用（与生理盐水安慰剂相比） 使用最初开发用于评估可卡因自我给药的人类实验室药物自我给药模型 （沃尔什等人，2001年），我们已经修改，以评估MA自我管理 假设：MA将产生比安慰剂和莫达非尼更大的主观和强化效应 治疗将减少MA的这些影响。 目标2.确定抑制控制（反应抑制）与MA自我给药之间的相关性。 莫达非尼对反应抑制、通过功能磁共振成像和结构磁共振成像的神经激活的影响将被 在项目1中评估。在项目2中，我们将测试反应抑制和MA自我给药之间的关联 行为与莫达非尼或安慰剂治疗期间。将评价MA自我给药 使用一种设计，在这种设计中，参与者必须抑制对MA的选择，以获得替代的选择 (i.e.,钱）。这些实验的结果将通过实验评估缺陷在抑制性细胞凋亡中的作用。 控制吸毒行为的功能。 假设：反应抑制将与MA的选择负相关（即，反应差 抑制将与MA自我给药增加相关）。

The overall goal of Project 2 is to establish linkages between fundamental research programs yielding mechanistic insights and a coordinated program of clinical research. We propose to assess the association between inhibitory control functioning (response inhibition) a behavioral function hypothesized to play an important role in addiction, and self-administration of MA by MA-dependent human volunteers in a laboratory setting. We will accomplish this goal by assessing the effects of modafinil, a medication known to enhance inhibitory control functioning, on MA self-administration using a human laboratory model of MA selfadministration. Aim 1. To determine the effects of modafinil treatment on self-administration of MA in a human laboratory model of MA self-administration. Following completion of Project 1 activities (a study of response inhibition and its neurobiological correlates in MA-dependent and control subjects), MA-dependent participants will enter Project 2. The timecourse of the subjective effects of MA following pretreatment with modafinil or placebo will be assessed using self-report rating scales ("high", "crave MA", etc.) because subjective effects of drugs frequently parallel their reinforcing effects. The reinforcing effects of MA (as compared to saline placebo) will be tested using a human laboratory model of drug self-administration originally developed to assess cocaine selfadministration (Walsh et al., 2001), which we have modified to assess MA self-administration Hypothesis: MA will produce greater subjective and reinforcing effects than placebo, and modafinil treatment will reduce these effects of MA. Aim 2. To determine the association between inhibitory control (response inhibition) and MA selfadministration. The effects of modafinil on response inhibition, neural activation via fMRI, and structural MRI will be assessed in Project 1. In Project 2, we will test the association between response inhibition and MA selfadministration behavior during treatment with modafinil or placebo. MA self-administration will be evaluated using a design in which participants must suppress choices for MA in order to receive alternative reinforcers (i.e., money). The outcome of these experiments will experimentally assess the role of deficits in inhibitory control functioning in drug-taking behavior. Hypothesis: Response inhibition will be inversely associated with choices for MA (i.e., poor response inhibition will be associated with increased MA self-administration).