Behavioral Momentum of Cocaine Self-Administration

描述（由申请人提供）：寻求药物的持续性和复发的趋势是药物滥用的定义特征。与使用毒品有关的线索被认为在寻求毒品的持续性和复吸中起着关键作用。药物寻找和服用是一种操作性行为，基于操作性条件反射原理的药物自我给药动物模型对研究药物寻找和复吸具有重要意义。因此，在研究的持续性的操作性行为的发展可能会提供洞察药物维持行为和复发的持续性。行为动量理论提供了一套方法和一个定量的理论，说明在刺激存在的情况下，强化条件如何影响操作性行为的持续性。基于行为动量理论的预测，我们发现，在刺激存在的情况下，酒精寻求的持续性取决于在该刺激存在的情况下可用的所有替代品（包括药物和非药物），即使其中一些替代品干扰酒精寻求。因此，可能有必要考虑所有的强化来源（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。扩展的方法和定量的理论框架的行为动量理论静脉注射可卡因自我管理可能会提供深入了解药物线索的存在下寻求药物的持久性。最近，我们的实验室已经实现了静脉注射可卡因自我管理程序与大鼠。该R21探索性发展补助金的目的是在我们的实验室中进一步开发大鼠静脉内可卡因自我给药，并将行为动力方法和理论扩展到可卡因自我给药。拟议的研究将研究可卡因线索存在下的强化条件如何有助于可卡因寻求的持续性和在其存在下复发的可能性。对这些问题的审查很重要，因为寻求毒品的持续性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会提供额外的工具，可以用于确定遗传和环境的贡献成瘾性疾病的动物模型。对药物线索如何影响药物寻求和复发的持续性的更正式的理解也可能建议针对减少暴露于此类线索的影响的新型行为和药理干预。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并可能复发。该项目的研究结果可能会提出新的行为治疗方法，以减少药物滥用的持续性和预防复发。

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.