Competition Between Conditioned Rewards: Novelty vs. Cocaine

描述（由申请人提供）：滥用药物的生理效应与吸毒环境中的线索之间形成的关联是吸毒行为获得、维持和复发的关键因素。由于这些条件联想对涉及药物奖励的选择行为施加了一定的控制，行为干预策略可能需要采用技术来减少条件药物奖励对选择行为的影响。例如，这些项目可能通过提供新的学习机会来与条件药物奖励竞争而受益。获得新奇奖励可能提供另一种学习历史，有可能与条件性可卡因奖励竞争。通过研究这项比赛，我们希望能促进综合药物滥用治疗方案的发展。因此，本提案的目标之一是测试学习历史的改变是否可以与条件药物奖励竞争，以控制选择行为。在这个应用程序中提出的实验将有助于实现我们的目标，通过系统地调查新奇条件奖励在多大程度上可以在可卡因剂量范围内与条件可卡因奖励竞争。我们还将评估未配对的可卡因暴露对这项比赛是否重要。此外，我们将决定是否新奇竞争可以维持一段时间。本次比赛将使用可卡因和新奇的场所调节程序进行调查。最初，用可卡因训练老鼠，让它们喜欢无偏位置条件反射装置的一侧。在接下来的阶段，一半的大鼠将会在它们原来未配对（没有药物）的那一侧反复接触一个新的物体。然后，两组人将在不同的日子里接受测试，以确定他们在无毒品状态和可卡因状态下的偏好。初步数据表明，在没有毒品的测试中，接触新奇事物可以使老鼠的偏好偏离与可卡因配对的环境，即使在随后的可卡因状态测试中，这种转变仍然存在。因此，新颖性的条件奖励效应改变了由药物奖励驱动的选择行为。我们预计，当可卡因配对线索维持在较高剂量时，这种竞争将持续下去，并且测试间隔更长。

DESCRIPTION (provided by applicant): The associations formed between the physiological effects of abused drugs and cues in the drug-taking environment are critical factors in the acquisition, maintenance, and relapse of drug-taking behavior. Because these conditioned associations exert some control over choice behaviors involving drug reward, behavioral intervention strategies may need to employ techniques to reduce the influence of conditioned drug reward over choice behaviors. For example, such programs may benefit by providing new learning opportunities to compete with conditioned drug reward. Access to novelty reward might provide an alternative learning history with the potential to compete with conditioned cocaine reward. By studying this competition, we hope to enhance the development of comprehensive drug abuse treatment programs. Therefore, one of the objectives of this proposal is to test whether a change in learning history can compete with conditioned drug reward for control over choice behavior. The experiments proposed in this application will help meet our goal by systematically investigating the extent to which novelty conditioned reward can compete with conditioned cocaine reward over a range of cocaine doses. We will also assess whether unpaired cocaine exposure is important for this competition. Additionally, we will determine whether novelty competition can be maintained over time. This competition will be investigated using a place conditioning procedure with cocaine and novelty. Initially, rats will be conditioned with cocaine to prefer one side of an unbiased place conditioning apparatus. In the subsequent phase, half of the rats will have repeated access to a novel object on their originally unpaired (no-drug) side. Both groups will then be tested on separate days for preference in a drug-free state and in the cocaine-drug state. Preliminary data indicates that access to novelty can shift a preference away from the cocaine-paired environment during drug-free testing and this shift remains even when rats are given an ensuing test in the cocaine-state. Thus, the conditioned rewarding effects of novelty changed choice behaviors motivated by drug reward. We expect that this competition will persist with higher doses of cocaine, when cocaine-paired cues are maintained, and at longer testing intervals.