Unpredictable drug and non-drug alternatives as determinants of cocaine choice

不可预测的药物和非药物替代品是可卡因选择的决定因素

• 批准号: 9097673
• 负责人: Sally Huskinson
• 金额: $ 6万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-20 至 2017-07-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9097673
• 关键词: Behavior; Behavior Therapy; Behavioral; Cocaine; Cocaine Abuse; Development; Dose; Drug Delivery Systems; Drug abuse; Food; Goals; Health; Human; Intake; Left; Location; Macaca mulatta; Modeling; Modification; Nature; Pharmaceutical Preparations; Price; Psychological reinforcement; Reinforcement Schedule; Research; Schedule; Self Administration; Time; base; contingency management; cost; drug abuser; experience; non-drug; novel; novel strategies; preference; psychosocial; reinforcer; response; substance abuse treatment; translational approach

DESCRIPTION (provided by applicant): The choice to take cocaine can be altered by manipulating the amount and responses required to obtain drug and non-drug alternatives, and this research has contributed to development of behavioral treatments for drug abuse, such as contingency management. Contingency management is the most effective psychosocial treatment for substance abuse. However, the feasibility of contingency management could be enhanced by reducing its cost. Using a nonhuman model of behavioral therapy, we can thoroughly examine variables such as response requirement and reinforcer amount to determine arrangements that most effectively reduce drug choice. Effects of such variables on drug choice in nonhumans have been studied primarily with qualitatively similar response-reinforcer relations for both options. However, the choice to take a drug when drug and competing non-drug alternatives are available under qualitatively different circumstances represents a more translational approach to what human drug abusers experience. Behavior is more persistent with unpredictable (e.g., variable) relative to predictable (e.g., fixed) schedules When choice is between fixed and variable schedules of food, nonhumans tend to choose the variable option, even when the result is net reinforcer loss. Whether nonhumans will choose a variable vs. fixed schedule of drug delivery has not been examined. The overall goal of the proposed research is to examine whether unpredictable reinforcement is a determinant of cocaine choice in rhesus monkeys. The significance of this research is two-fold: 1) it will establish the extent to which a fundamental behavioral phenomenon-preference for unpredictable options-is a key feature of cocaine self-administration; 2) confirmation of our hypotheses would support the use of novel and easily implemented modifications to behavioral therapy for drug abuse based on the unpredictable nature of drug and non-drug options. Specific Aim 1 is to examine choice between predictable and unpredictable schedules of cocaine. It is hypothesized that cocaine will be a more effective reinforcer when available in an unpredictable situation. Specific Aim 2 is to examine choice between predictable and unpredictable schedules of cocaine and food delivery in a drug vs. food situation. It is hypothesized that cocaine will be more effective when it is available under an unpredictable schedule and less effective when food is available under and unpredictable schedule. Specific Aim 3 is to examine choice between cocaine and food when food is unpredictable in terms of schedule and amount per delivery. It is hypothesized that food will be more effective when its schedule and amount of delivery are unpredictable relative to situations where only schedule or amount is unpredictable. If cocaine is chosen more robustly under unpredictable situations, then the unpredictability of cocaine may serve to increase its reinforcing value. Conversely, reducing cocaine choice when alternative non-drug reinforcers are unpredictable may provide an effective and novel approach to treating cocaine abuse.

描述（由申请人提供）：可以通过控制获得药物和非药物替代品所需的量和反应来改变服用可卡因的选择，这项研究有助于开发药物滥用行为治疗方法，例如应急管理。应急管理是药物滥用最有效的心理社会治疗方法。然而，可以通过降低成本来增强应急管理的可行性。使用行为治疗的非人类模型，我们可以彻底检查反应要求和强化剂量等变量，以确定最有效地减少药物选择的安排。这些变量对非人类药物选择的影响主要是通过两种选择的性质相似的反应-强化关系来研究的。然而，当药物和竞争性非药物替代品在性质不同的情况下可用时，选择服用药物代表了对人类药物滥用者经历的一种更具转化性的方法。相对于可预测的（例如固定的）时间表，不可预测的（例如可变的）行为更持久。当在固定和可变的食物时间表之间进行选择时，非人类倾向于选择可变的选项，即使结果是净强化物损失。非人类是否会选择可变与固定的药物输送时间表尚未得到检验。该研究的总体目标是检验不可预测的强化是否是恒河猴选择可卡因的决定因素。这项研究的意义有两个：1）它将确定基本行为现象（对不可预测的选择的偏好）在多大程度上是可卡因自我给药的一个关键特征； 2）我们的假设的确认将支持基于药物和非药物选择的不可预测性，对药物滥用行为疗法使用新颖且易于实施的修改。具体目标 1 是检查可卡因的可预测和不可预测的时间表之间的选择。据推测，在不可预测的情况下使用可卡因将是一种更有效的强化剂。具体目标 2 是检查在药物与食物情况下可卡因和食物输送的可预测和不可预测时间表之间的选择。据推测，当在不可预测的时间表下获得可卡因时，可卡因将更有效，而当在不可预测的时间表下获得食物时，可卡因将不太有效。具体目标 3 是当食物的时间表和每次交付的数量无法预测时，检查可卡因和食物之间的选择。据推测，相对于仅时间表或数量不可预测的情况，当其递送的时间表和数量不可预测时，食物将更有效。如果在不可预测的情况下更稳健地选择可卡因，那么可卡因的不可预测性可能会增加其强化价值。相反，当替代的非药物强化剂不可预测时，减少可卡因的选择可能会为治疗可卡因滥用提供有效且新颖的方法。