Competition Between Conditioned Rewards: Novelty vs. Cocaine

描述（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。由于这些条件性联想对涉及药物奖赏的选择行为具有一定的控制作用，因此行为干预策略可能需要采用技术来减少条件性药物奖赏对选择行为的影响。例如，这些计划可能会受益于提供新的学习机会，以与条件性药物奖励竞争。获得新奇奖励可能提供一种替代的学习历史，具有与条件可卡因奖励竞争的潜力。通过研究这次比赛，我们希望加强全面的药物滥用治疗计划的发展。因此，本提案的目标之一是测试学习历史的变化是否可以与条件性药物奖励竞争对选择行为的控制。在本申请中提出的实验将有助于实现我们的目标，系统地调查在何种程度上新奇的条件奖励可以竞争条件可卡因奖励的可卡因剂量范围内。我们还将评估未配对的可卡因暴露是否对这种竞争很重要。此外，我们将确定是否可以随着时间的推移保持新奇的竞争。这场比赛将使用可卡因和新奇的地方条件反射程序进行调查。最初，将用可卡因使大鼠条件化以偏好无偏位置条件化装置的一侧。在随后的阶段，一半的大鼠将在其最初未配对（无药物）的一侧重复访问新物体。然后，两组将在不同的日子进行测试，以确定在无药物状态和可卡因药物状态下的偏好。初步数据表明，在无药物测试期间，获得新奇可以将偏好从可卡因配对环境中转移出来，即使在可卡因状态下对大鼠进行后续测试，这种转移仍然存在。因此，新奇性的条件性奖赏效应改变了药物奖赏激发的选择行为。我们预计，这种竞争将持续与更高剂量的可卡因，可卡因配对线索时，保持，并在更长的测试间隔。

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.