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

描述(由申请人提供)：服用可卡因的选择可以通过操纵获得药物和非药物替代品所需的数量和反应来改变，这项研究有助于药物滥用行为治疗的发展，如应急管理。应急管理是治疗药物滥用的最有效的心理社会治疗方法。然而，应急管理的可行性可以通过降低其成本来提高。使用行为疗法的非人类模型，我们可以彻底检查反应要求和增强剂数量等变量，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定性相似的反应-强化关系来研究的。然而，当药物和竞争的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吸毒者经历的一种更具翻译性的方法。不可预测(例如，可变)的行为比可预测(例如，固定)的时间表更持久。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，即使结果是净增强剂损失。非人类是否会选择可变的给药程序和固定的给药程序还没有被研究过。这项拟议研究的总体目标是检查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方面：1)它将确定一个基本的行为现象--对不可预测的选择的偏好--在多大程度上是可卡因自我管理的关键特征；2)我们的假设得到证实，将支持基于药物和非药物选择的不可预测的性质，对药物滥用行为治疗使用新颖且易于实施的修改。具体目标1是审查可卡因的可预测和不可预测时间表之间的选择。据推测，在不可预测的情况下，可卡因将是一种更有效的增强剂。具体目标2是研究在药物和食物的情况下，可卡因和食物递送的可预测和不可预测时间表之间的选择。假设可卡因在不可预测的时间表下可用时会更有效，而在食物可在不可预测的时间表下可用时效果较差。具体目标3是审查在食物的时间表和每次运送的数量方面无法预测的情况下，在可卡因和食物之间的选择。人们假设，与只有时间表或数量不可预测的情况相比，当食物的时间表和送货量不可预测时，食物将更有效。如果在不可预测的情况下更坚定地选择可卡因，那么可卡因的不可预测性可能有助于增加其强化价值。相反，在其他非药物增强剂不可预测的情况下减少可卡因的选择，可能会为治疗可卡因滥用提供一种有效的新方法。

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.