Temporal Discounting of Punishment of Drug Choice

药物选择惩罚的时间贴现

• 批准号: 7695966
• 负责人: William L. Woolverton
• 金额: $ 14.8万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7695966
• 关键词: Animal Model; Attention; Behavior; Catheters; Cocaine; Data; Dose; Drug Controls; Drug abuse; Drug usage; Effectiveness; Goals; Health; Histamine; Human; Implant; Imprisonment; Infusion procedures; Injection of therapeutic agent; Methods; Modeling; Monkeys; Nature; Pharmaceutical Preparations; Play; Psychological reinforcement; Punishment; Rattus; Relative (related person); Reporting; Research; Role; Self Administration; Shock; Smoker; Smoking; Solutions; Techniques; Testing; Use Effectiveness; base; design; discount; discounting; drug of abuse; hangover; high risk; innovation; mathematical model; programs; public health relevance; reinforcer

DESCRIPTION (provided by applicant): Imposing a delay between a behavior and its reinforcer weakens the effectiveness of that reinforcer and decreases its subjective value, a phenomenon referred to as temporal discounting. There is a well-established mathematical model, the hyperbolic discounting function, that describes temporal discounting. Recent research with temporal discounting has made substantial theoretical contributions to our understanding of drug abuse. Imposing a delay between a behavior and a punisher can also diminish the effectiveness of the punisher. The discounting of delayed punishers is particularly relevant to the choice to take a drug of abuse. We often expect negative consequences of drug taking to function as punishers to suppress drug taking. However, these consequences (if they occur at all) are delayed relative to the drug effect, and this delay likely diminishes their effectiveness. Empirical data concerning the actual functional relationship between a delayed punisher and the choice to take a drug of abuse is very limited. Recent research with non-humans has contributed to our understanding of the effects of delayed reinforcement on drug choice. However, no information is available on the effects of delayed punishment on drug taking by non-humans. The overall goal of the present proposal is to examine how imposing a delay between cocaine injections and subsequent punishment alters the ability of that punishment to decrease the likelihood of cocaine self-administration. The proposal has two Specific Aims, each approaching the question from a slightly different perspective. For both Aims we will use a method we developed to study punishment of drug choice by histamine injection. Specific Aim 1 is to examine the relationship between delay of punishment and its effectiveness using a choice between a fixed dose of cocaine followed by different injections of histamine. Our hypotheses are that the effectiveness of punishment of drug choice will be diminished with delay to a histamine injection and that the decrease in effectiveness will be well described by a hyperbolic discounting function. Specific Aim 2 is to examine the relationship between delay of punishment and its effectiveness using a choice between a fixed dose of histamine that follows various doses of cocaine. Our hypotheses are as in Specific Aim 1: the effectiveness of punishment of drug choice will be diminished with delay to a histamine injection and this decrease in effectiveness will be well described by a hyperbolic discounting function. The research in the present proposal will adapt the innovative technique of using an aversive drug infusion to punish self-administration in order to test the hypothesis that the effectiveness of punishment diminishes as a decreasing hyperbolic function of delay to its presentation. An animal model will be particularly useful to push the parametric envelope and begin to establish a conceptual framework within which to understand the control of drug taking by punishment. PUBLIC HEALTH RELEVANCE: We expect negative consequences of drug taking, for example hangover or incarceration, to decrease drug taking. However, negative consequences of drug taking are often delayed in a manner that decreases their effectiveness and may, thereby, contribute to escalating drug abuse. The present project is designed to establish the relationship between the delay to a negative consequence of drug taking and its effectiveness in decreasing the choice to take a drug.

描述（由申请人提供）：在行为及其增强器之间施加延迟，削弱了增强剂的有效性并降低其主观价值，这一现象称为时间折扣。有一个完善的数学模型，即双曲线折现功能，描述了时间折扣。暂时折扣的最新研究为我们对药物滥用的理解做出了实质性的理论贡献。施加行为和惩罚者之间的延迟也可以降低惩罚者的有效性。延迟惩罚者的折扣与选择服用滥用药物的选择特别相关。我们经常期望吸毒的负面后果作为惩罚者抑制药物服用。但是，这些后果（如果完全发生）相对于药物效应延迟，这种延迟可能会降低其有效性。关于延迟惩罚者与服用滥用药物的选择之间的实际功能关系的经验数据非常有限。非人类的最新研究有助于我们理解延迟增强对药物选择的影响。但是，没有关于延迟惩罚对非人类服药的影响的信息。本提案的总体目标是检查可卡因注射和随后的惩罚之间的延迟如何改变了这种惩罚减少可卡因自我管理的可能性的能力。该提案有两个具体的目标，每个目标都从略有不同的角度来到了问题。对于这两种目标，我们将使用我们开发的一种方法来研究组胺注射对药物选择的惩罚。具体目的1是使用固定剂量可卡因之间的选择，然后在组胺上注射不同的注射剂量之间的选择，以检查延迟的延迟与其有效性之间的关系。我们的假设是，对组胺注射的延迟，对药物选择的惩罚的有效性将降低，并且有效性的降低将通过双曲线折现功能很好地描述。具体目的2是使用固定剂量的组胺之间的选择来检查延迟惩罚与其有效性之间的关系，该组胺遵循各种可卡因剂量。我们的假设与特定的目标1一样：延迟对组胺注射的惩罚有效性将降低，而双曲线折现功能将很好地描述有效性的降低。本提案中的研究将适应创新的技术，即使用厌恶的药物输液来惩罚自我管理，以检验以下假设，即惩罚的有效性会降低，因为延迟的延迟功能降低了其表现。动物模型对于推动参数包络并开始建立一个概念框架特别有用，在该概念框架中，可以在其中理解对药物对惩罚的控制。公共卫生相关性：我们预计吸毒的负面影响，例如宿醉或监禁，可以减少药物服用。但是，服用药物的负面后果通常会以降低其有效性的方式延迟，从而导致滥用毒品。本项目旨在建立延迟服用药物的负面后果与减少药物选择的有效性之间的关系。