Behavioral Momentum of Cocaine Self-Administration

描述（由申请人提供）：持续寻求药物的本质和复发的倾向是药物滥用的决定性特征。与使用药物有关的线索被认为在持续寻求药物和复发中起着关键作用。寻找和服用药物是一种操作性行为，基于操作性条件反射原理的药物自我给药动物模型有助于研究药物寻找和复发。因此，对操作性行为持续性研究的进展可能为药物维持行为的持续性和复发提供见解。行为动量理论提供了一套方法和定量理论来解释强化条件如何在刺激存在的情况下影响操作性行为的持久性。基于对行为动量理论的预测，我们发现，在刺激存在的情况下，寻求酒精的持久性取决于在刺激存在的情况下所有可用的强化物（包括药物和非药物），即使其中一些强化物干扰了寻求酒精。因此，可能有必要考虑与药物线索相关的所有强化来源（即药物和非药物），以了解该线索对治疗期间和治疗后药物寻求持续性的影响。将行为动量理论的方法和定量理论框架扩展到静脉注射可卡因自我给药，可能会对药物线索存在下药物寻找的持久性提供见解。最近，我们的实验室在大鼠身上实施了静脉注射可卡因的自我给药程序。这项R21探索性发展资助的目的是在我们的实验室中进一步发展大鼠静脉注射可卡因自我给药，并将行为动量方法和理论扩展到可卡因自我给药。拟议的研究将检验在可卡因线索存在的情况下，强化条件如何促进可卡因寻求的持久性和在可卡因线索存在的情况下复发的可能性。审查这些问题很重要，因为持续寻求药物是药物滥用的一个决定性特征。本文提出的方法的进一步发展可能提供额外的工具，可用于识别动物模型中成瘾障碍的遗传和环境贡献。对药物线索如何影响药物寻找的持久性和复发的更正式的理解也可能提出新的行为和药理学干预措施，旨在减少暴露于此类线索的影响。公共卫生相关性：该项目对公共卫生很重要，因为它将有助于我们了解药物和非药物奖励如何使药物滥用如此持久和可能复发。这个项目的发现可能会提出新的行为治疗方法，以减少药物滥用的持久性和防止复发。

DESCRIPTION (provided by applicant): The persistent nature of drug seeking and the tendency to relapse are defining features of drug abuse. Cues associated with using drugs are thought to play a critical role in the persistence of drug seeking and in relapse. Drug seeking and taking are operant behavior and animal models of drug self-administration based on the principles of operant conditioning have been useful for studying drug seeking and relapse. Thus, developments in the study of the persistence of operant behavior may provide insights into the persistence of drug-maintained behavior and relapse. Behavioral momentum theory has provided a set of methods and a quantitative theory of how reinforcement conditions affect the persistence of operant behavior in the presence of a stimulus. Based on a prediction of behavioral momentum theory, we have found that the persistence of alcohol seeking in the presence of a stimulus depends on all the reinforcers (both drug and non-drug) available in the presence of that stimulus, even if some of those reinforcers interfere with alcohol seeking. Thus, it may be necessary to consider all of the sources of reinforcement (i.e., drug and non-drug) associated with a drug cue to understand the impact of that cue on the persistence of drug seeking during and after treatment. Extensions of the methods and quantitative theoretical framework of behavioral momentum theory to intravenous cocaine self-administration may provide insights into the persistence of drug seeking in the presence of drug cues. Recently, our laboratory has implemented intravenous cocaine self-administration procedures with rats. The purpose of this R21 Exploratory Developmental Grant is to further develop intravenous cocaine self-administration with rats in our laboratory and to extend behavioral momentum methods and theorizing to cocaine self- administration. The proposed research will examine how the conditions of reinforcement in the presence of cocaine cues contribute to the persistence of cocaine seeking and likelihood of relapse in their presence. Examination of these issues is important because the persistence of drug seeking is a defining feature of drug abuse. The further development of the methods proposed here may provide additional tools that could be useful for identifying genetic and environmental contributions to addictive disorders within animal models. A more formal understanding of how drug cues impact the persistence of drug seeking and relapse may also suggest novel behavioral and pharmacological interventions targeted at reducing the impact of exposure to such cues. PUBLIC HEALTH RELEVANCE: This project is important to public health because it will contribute to our understanding of how drug and non-drug rewards make drug abuse so persistent and likely to relapse. Findings from this project may suggest novel behavioral treatments targeted at reducing the persistence of drug abuse and preventing relapse.