Reinforcer efficacy: measures and neural mechanisms

描述（由申请人提供）：对人类延迟折扣的研究表明，吸毒者对小的、立即的、延迟的奖励有一种夸大的偏好，即使即时奖励远远小于延迟奖励。这些研究被解释为意味着吸毒者比非吸毒者更冲动，并且可能吸毒改变了个人评估与奖励相关的收益和成本的过程。这些过程被认为决定了药物和非药物控制行为的效力。然而，除了延迟之外，还有其他成本，可能会导致延迟者的价值打折扣。两种成本是不确定性和努力。建议进行五项研究，以使用主要研究者及其同事开发的用于大鼠的贴现程序来评估所有三种成本对药物疗效的影响（延迟收到奖励、收到奖励的不确定性以及获得奖励所需的努力）。基本假设是：1）对延迟奖励折扣更高的大鼠也会对不确定和努力的奖励折扣更高; 2）对三种不同类型的成本的折扣将受到一系列行为和药理学操作的类似影响。实验1通过评估延迟折扣、不确定性折扣和努力折扣在同一动物中的相关性，确定大鼠是否将大的、昂贵的奖励折扣到类似的程度，而不管成本类型如何，并检查慢性注射尼古丁对折扣的影响。实验2考察了奖励的大小如何影响延迟、不确定性和努力折扣。实验3确定是否偏好开关从小，便宜的奖励，大，昂贵的奖励时，两个选项都增加了固定的成本。实验4考察了高成本条件下是否会导致延迟、不确定性和努力折扣的减少。实验5研究多巴胺在调节延迟、不确定性和努力折扣中的作用。这些研究将提供有关大脑评估药物疗效时所考虑的变量以及可用于改变药物疗效的程序的信息，这两者都将对药物滥用治疗产生影响。此外，在这些研究中收集的数据将为未来的研究提供基础，这些研究将检查个体如何评估药物价值的差异是否与药物使用和滥用的开始，进展和停止有因果关系。

DESCRIPTION (provided by applicant): Studies of delay discounting in humans have revealed that drug users have an exaggerated preference for small, immediate over large, delayed rewards, even when the immediate reward is substantially smaller than the delayed reward. These studies have been interpreted to mean that drug users are more impulsive than nonusers and, possibly, that drug use has altered the processes by which individuals evaluate the benefits and costs associated with rewards. These processes are believed to determine the efficacy of drug and nondrug reinforcers to control behavior. However there are costs other than delay which can cause the value of a reinforcer to be discounted. Two such costs are uncertainty and effort. Five studies are proposed to evaluate the impact of all three costs on reinforcer efficacy (delay to the receipt of a reward, uncertainty about the receipt of the reward, and the effort required to obtain the reward) using a discounting procedure that was developed by the Principal Investigator and her colleague for use with rats. The basic hypotheses are that 1) the rats that discount delayed rewards more will also discount uncertain and effortful rewards more and 2) that discounting for the three different types of cost will be similarly effected by a series of behavioral and pharmacological manipulations. Experiment 1 determines whether rats discount large, expensive rewards to similar degrees regardless of the cost type by assessing the correlation between delay discounting, uncertainty discounting and effort discounting in the same animals, and examines the impact of chronic injections of nicotine on discounting. Experiment 2 examines how the magnitude of reward affects delay, uncertainty and effort discounting. Experiment 3 determines whether preference switches from the small, cheaper reward to the large, expensive reward when a fixed cost is added to both alternatives. Experiment 4 examines whether exposure to high-reinforcer-cost conditions leads to decreases in delay, uncertainty and effort discounting. Experiment 5 investigates the role of dopamine in modulating delay, uncertainty and effort discounting. These studies will provide information about the variables taken into account when the brain evaluates reinforcer efficacy and procedures that can be used to alter reinforcer efficacy, both of which will have implications for drug abuse treatment. Further, the data collected in these studies will provide a basis for future studies, which will examine whether differences in how individuals evaluate the value of reinforcers are causally related to the initiation, progression and cessation of drug use and abuse.