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联系是吸毒行为获得、维持和复发的关键因素。由于这些条件性联系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使用技术来减少条件药物奖励对选择行为的影响。例如，这些计划可能会通过提供新的学习机会来与有条件的药物奖励竞争而受益。获得新奇奖励可能会提供另一种学习历史，有可能与条件可卡因奖励竞争。通过对本次比赛的研究，我们希望能够促进药物滥用综合治疗方案的发展。因此，这项提议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。本申请中提出的实验将通过系统地调查新奇条件奖励在一定剂量范围内与条件可卡因奖励竞争的程度来帮助实现我们的目标。我们还将评估未配对的可卡因接触对这场比赛是否重要。此外，我们将确定新颖性竞争能否长期保持下去。这场比赛将使用可卡因和新奇玩意儿的位置调节程序进行调查。最初，大鼠将被给予可卡因条件反射，以偏爱无偏向的位置调节装置的一侧。在接下来的阶段中，一半的老鼠将重复接触到它们最初未配对的(不含药物的)一侧的新物体。然后，这两组人将在不同的日子接受无毒状态和可卡因-毒品状态下的偏好测试。初步数据表明，在无毒品测试期间，获取新奇事物可以改变对与可卡因配对的环境的偏好，即使在可卡因状态下对大鼠进行随后的测试，这种转变仍然存在。因此，新颖性的条件性奖赏效应改变了药物奖赏所激发的选择行为。我们预计，当维持与可卡因配对的线索时，这场竞争将持续更高剂量的可卡因，并以更长的测试间隔进行。

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.