Theory of Resurgence of Cocaine Seeking

描述（由申请人提供）：复发是药物成瘾的典型特征之一，可由多种事件引起，如接触药物、药物提示或压力。服药是一种操作性行为，人类滥用药物对动物自我给药过程起强化作用。在实验室中，非药物强化物的可用性降低了药物自我给药，而明确安排替代非药物强化物的行为干预是治疗药物成瘾最成功的方法之一。然而，当这种治疗结束并且不再提供替代强化剂时，复发是常见的。此外，治疗外非药物强化的丧失可能更普遍地在压力相关复发中起作用。虽然现有的复发动物模型对检查复发机制有用，但它们没有检查由替代行为的强化丧失引起的复发。我们已经证明，操作性条件反射中的另一种复发现象“复发”可以提供一种有用的动物模型，用于替代强化丧失引起的药物复发。死灰复燃是指在灭绝期间加强的另一种行为随后也被置于灭绝状态时，一种已消失的操作性行为的再现。我们已经证明了消失的可卡因在老鼠自我给药中的复苏，并开发了一个复苏的定量模型，它很好地解释了现有的关于食物维持行为复苏的数据。该理论已被证明在临床治疗中是有用的，使用替代强化来减少发育障碍儿童的问题行为，但尚未在药物寻找的背景下进行检验。这个R21 CEBRA项目将把这一理论应用于成瘾研究。具体目标1检查了关于药物强化和替代强化如何在复发的产生中相互作用的理论的核心预测。该理论预测，当替代强化物被移除时，更频繁或更大的替代强化物会产生更大的复发。有一些证据表明，在治疗期间接受较大代金券的患者比使用较小代金券获得类似戒断水平的患者更有可能复发。因此，除了在

DESCRIPTION (provided by applicant: Relapse is one of the defining features of drug addiction and can be precipitated by a variety of events such as exposure to drugs, drug cues, or stress. Drug taking is operant behavior, and drugs abused by humans function as reinforcers for animals in drug self-administration procedures. Availability of non-drug reinforcement decreases drug self-administration in the laboratory, and behavioral interventions explicitly arranging alternative non-drug reinforcers have been some of the most successful treatments for drug addiction. However, relapse is common when such treatment ends and the alternative reinforcers are no longer provided. Furthermore, loss of non-drug reinforcement outside of treatment might play a role in stress-related relapse more generally. Although existing animal models of relapse are useful for examining the mechanisms of relapse, they do not examine relapse induced by loss of reinforcement for alternative behavior. We have shown that "resurgence", another relapse phenomenon in operant conditioning, can provide a useful animal model of drug relapse induced by loss of alternative reinforcement. Resurgence refers to the reappearance of an extinguished operant behavior when an alternative behavior reinforced during extinction is also subsequently placed on extinction. We have demonstrated resurgence of extinguished cocaine self-administration of rats and have developed a quantitative model of resurgence that does a good job accounting for the existing data on resurgence of food-maintained behavior. The theory has proven useful in translation to clinical treatments using alternative reinforcement to reduce problem behavior of children with development disabilities, but has not been examined within the context of drug seeking. This R21 CEBRA project will adapt this theory to addictions research. Specific Aim 1 examines core predictions of the theory about how drug reinforcement and alternative reinforcement interact in the production of relapse. The theory predicts that more frequent or larger alternative reinforcers produce greater relapse when alternative reinforcement is removed. There is some evidence that patients receiving larger vouchers during treatment are more likely to relapse than those achieving similar levels of abstinence with smaller vouchers. Thus, in addition to serving a critical role in adapting the theory to addictions research, completion of this aim could also show how the theory might be useful for informing future interventions for substance abuse. Specific Aim 2 examines two predictions of the theory about how relapse induced by loss of alternative non-drug reinforcement might be reduced. Completion of aim this will serve a critical role in examining the predictive validity of the theory for drug seeking and evaluate its utility in generating novel hypotheses about how relapse might be reduced.