Adolescent Cocaine Abuse: Electrophysiology & Behavior

描述(由申请人提供)：目前的提案比较了青少年和成年大鼠在服用可卡因前后的情况，以评估是否固有的或药物诱导的多巴胺细胞活动变化可能导致青少年成瘾倾向。目前正在申请《康复法案》的资金，以扩大当前项目的范围，将压力作为可能影响青少年成瘾倾向的一个因素。压力在药物成瘾中起着关键作用，并可能通过影响多巴胺的传递来增强成瘾的易感性。目前尚不清楚青少年和成年人对压力的这些影响是否有不同的敏感性，或者青春期和成年期的药物暴露是否会不同地改变随后的压力反应。这些都是重要的问题，因为在压力和药物诱导的神经适应方面与年龄相关的差异可能是青少年和成年人在药物自我管理和复发易感性方面的差异的基础。 解决这些问题的具体目标是：确定青春期和成年大鼠是否存在差异 该研究的目的是研究对应激引起的药物摄入量和多巴胺细胞活性增加的敏感性(目标1)，并确定与成年相比，如果在青春期经历过药物，大鼠是否更容易出现应激引起的复发和多巴胺细胞活动增加(目标2)。这两个目标都回答了关于压力和药物相关行为之间的相互作用以及多巴胺细胞在这些影响中的潜在作用的重要和独立的问题。重要的是，它们将帮助我们了解压力的影响是受到经历压力的年龄的影响，还是受到经历药物的年龄的影响。这一修订将加速朝着了解压力如何影响青少年成瘾倾向这一重要目标取得进展。这是一个重要的话题，符合NIDA的目标，即征集整合环境和发展变量的研究，以便更好地了解药物成瘾。这一修订也符合《复苏法案》的目标，因为它将通过雇佣和留住工作人员来刺激经济。具体地说，资金将用于支持一名新生并保留一名优秀的研究技术员，如果不是这样，她的职位将在2009年秋季被解雇，因为她是利用2009年夏秋季即将结束的启动基金聘用的。此外，这一修订还有望通过为我们的可操作的自我管理笼子购买新的部件来刺激经济，这些部件是执行本申请中提议的实验所必需的。 公共卫生相关性：这些研究考察了压力和多巴胺在青少年成瘾倾向中的作用。他们在动物模型中使用了一种成熟的技术的新组合，以更好地了解青少年成瘾的病因。从长远来看，这些研究将为制定可以防止成瘾和吸毒复发的治疗策略提供新的见解。

DESCRIPTION (provided by applicant): The current proposal compares adolescent and adult rats, both before and after cocaine self-administration, to appraise whether inherent or drug-induced changes in dopamine cell activity could underlie adolescent addiction liability. Recovery Act funds are being requested to expand the scope of the current project by adding stress as a possible factor that could influence adolescent addiction liability. Stress plays a critical role in drug addiction and may enhance addiction liability via its effects on dopamine transmission. It is unknown whether adolescents and adults are differentially sensitive to these effects of stress, or if drug exposure during adolescence vs. adulthood differentially modifies subsequent reactivity to stress. These are important questions because age-related differences in stress- and drug-induced neuroadaptations could underlie differences between adolescents and adults in susceptibility to drug self-administration and relapse. Specific aims to address these questions are: to determine if adolescent and adult rats are differentially sensitive to stress-induced increases in drug intake and dopamine cell activity (Aim 1), and to determine if rats are more susceptible to stress-induced relapse and increases in dopamine cell activity if they experienced drugs during adolescence vs. adulthood (Aim 2). Both aims answer important and independent questions about the interaction between stress and drug associated behaviors, and the potential role of dopamine cells in these effects. Importantly, they will help us understand if the effects of stress are influenced by the age at which the stress is experienced or if they are influenced by the age at which the drug is experienced. This revision will accelerate progress towards the important goal of understanding how stress could impact adolescent addiction liability. This is an important topic that that fits into NIDA's goal to solicit research that integrates environmental and developmental variables in order to have a better understanding of drug addiction. This revision also fits into the objectives of the Recovery Act, as it will stimulate the economy by enabling the hiring and retention of staff. Specifically, funds will be used to support a new student and to retain an excellent Research Technician whose position would otherwise be terminated fall 2009, given that she was hired on startup funds that are ending summer/fall 2009. In addition, this revision is also expected to stimulate the economy by enabling the purchase of new components for our operant self-administration cages, which are necessary to perform the experiments proposed in this application. PUBLIC HEALTH RELEVANCE: These studies examine the role of stress and dopamine in adolescent addiction liability. They use a novel combination of well-established techniques in animal models to provide a better understanding of the etiology of adolescent addiction. In the long run, these studies will offer new insights into the development of treatment strategies that could prevent the development of addiction and relapse to drug taking.