Theory of Resurgence of Cocaine Seeking

描述(由申请人提供：复发是吸毒成瘾的特征之一，可由各种事件引起，如接触毒品、毒品线索或压力。吸毒是一种可操作性行为，人类滥用的药物在药物自我给药过程中对动物起到了增强剂的作用。非药物增强剂的可获得性减少了实验室中的药物自我给药，明确安排替代非药物增强剂的行为干预一直是治疗药物成瘾最成功的方法之一。然而，当这种治疗结束，不再提供替代增强剂时，复发是常见的。此外，在治疗之外失去非药物强化可能在更普遍的应激相关复发中起作用。虽然现有的复发动物模型对研究复发的机制很有用，但它们并没有研究由于缺乏对替代行为的强化而导致的复发。我们已经证明，操作性条件反射中的另一种复发现象“复燃”可以提供一种有用的动物模型，研究由替代强化缺失引起的药物复发。复活指的是当在灭绝过程中强化的另一种行为随后也被置于灭绝状态时，一种已熄灭的可操作行为的再现。我们已经证明了熄灭的可卡因自身给药大鼠的复苏，并开发了一个复苏的量化模型，该模型很好地解释了现有的关于食物维持行为复苏的数据。这一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，但尚未在寻求药物的背景下进行检验。这个R21 CEBRA项目将把这一理论应用于成瘾研究。具体目标1检验了关于药物强化和替代强化如何在复发产生中相互作用的理论的核心预测。该理论预测，当替代强化被移除时，更频繁或更大的替代强化会导致更大的复发。有一些证据表明，在治疗期间接受较大代金券的患者比那些获得类似程度戒酒的患者更有可能复发。因此，除了在 将该理论应用于成瘾研究，完成这一目标还可以表明，该理论可能有助于指导未来对药物滥用的干预。具体目标2检验了该理论的两个预测，即如何减少因失去替代非药物强化而导致的复发。目标的完成这将在检验药物寻找理论的预测有效性和评估其在如何减少复发的新假说中的有效性方面发挥关键作用。

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.