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，可卡因自我给药前后，以评估多巴胺细胞活性的固有或药物诱导的变化是否可能是青少年成瘾倾向的基础。正在要求《恢复法》提供资金，以扩大目前项目的范围，增加压力，作为可能影响青少年成瘾责任的一个可能因素。压力在药物成瘾中起着关键作用，并可能通过其对多巴胺传递的影响增强成瘾倾向。目前尚不清楚青少年和成年人是否对这些压力的影响有不同的敏感性，或者青春期与成年期的药物暴露是否会改变随后对压力的反应。这些都是重要的问题，因为年龄相关的差异，压力和药物诱导的神经适应可能是青少年和成人之间的差异，在药物自我管理和复发的易感性。 解决这些问题的具体目标是：确定青少年和成年大鼠是否存在差异 对应激诱导的药物摄入量和多巴胺细胞活性增加敏感（目标1），并确定如果大鼠在青春期与成年期经历药物，是否更容易受到应激诱导的复发和多巴胺细胞活性增加的影响（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相互作用的重要和独立的问题，以及多巴胺细胞在这些影响中的潜在作用。重要的是，它们将帮助我们了解压力的影响是否受到经历压力的年龄的影响，或者是否受到经历药物的年龄的影响。这一修订将加速实现理解压力如何影响青少年成瘾倾向的重要目标。这是一个重要的主题，符合NIDA的目标，征求研究，整合环境和发展变量，以更好地了解吸毒成瘾。这一修订也符合《复苏法》的目标，因为它将通过雇用和留住工作人员来刺激经济。具体而言，资金将用于支持一名新学生，并保留一名优秀的研究技术员，否则她的职位将在2009年秋季终止，因为她是在2009年夏季/秋季结束的启动资金上被聘用的。此外，该修订还有望通过为我们的操作性自我给药笼购买新组件来刺激经济，这是进行本申请中提出的实验所必需的。 公共卫生相关性：这些研究探讨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新颖的成熟技术组合，以更好地了解青少年成瘾的病因。从长远来看，这些研究将为制定预防吸毒成瘾和复吸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.