Incubation of craving: Abstinence and Environmental Enrichment-mediated Molecula

描述(由申请人提供)：重新吸毒和寻食是一个重大的公共卫生问题，因为过度关注毒品或食物寻觅和服用会导致许多负面的健康后果。这项应用使用了一种寻找奖赏的老鼠模型，目的是确定在短期或长期禁欲条件下，有蔗糖自我给药史的大鼠大脑中的基因表达模式，这些条件分别会产生低水平或高水平的奖赏寻求(“渴望的孵化”)。此外，一些大鼠将在丰富的环境中经历禁欲，我们之前已经演示过一种操作，以减弱寻求蔗糖的孵化。第一个目标是使用Fos免疫组织化学方法绘制蔗糖线索激活区，以可视化基因表达。目的2将利用这种图谱信息集中在离散的大脑区域来分离和定量多巴胺D1受体信号级联蛋白，其中一些处于基础状态和磷酸化状态，因为我们发现D1受体拮抗作用在蔗糖寻找中具有时间依赖(孵育依赖)的效应。除了识别成瘾的神经底物作为提供新的成瘾疗法的一种手段之外，这些研究还将作为一种让本科生研究人员接触科学过程的手段来进行。通过这种方式让学生参与进来，将增强他们在西华盛顿大学的培训经验和研究环境。 与公共卫生相关：重新吸毒或寻找食物是一个重大的公共卫生问题，因为过度关注和消费毒品和食物会导致许多负面的健康后果。这些研究旨在确定在延长丰富的环境生活条件下进行或不进行复发减毒预治疗的情况下，与复发行为相关的大鼠大脑中的差异基因表达。这些研究的结果可能有助于更好地理解复发行为的分子生物学，从而促进新的复发治疗方法的发展。

DESCRIPTION (provided by applicant): Relapse to drug and food seeking presents a significant public health concern as excessive preoccupation with drug or food seeking and taking contributes to numerous negative health outcomes. Using a rat model of reward seeking, this application aims to identify gene expression patterns in the brains of rats with a history of sucrose self-administration under short or long-term abstinence conditions known to produce low or high levels, respectively, of reward seeking ("incubation of craving"). In addition, some rats will experience abstinence in an enriched environment, a manipulation we have previously demonstrated to attenuate incubation of sucrose seeking. Gene expression will be visualized in the first Aim using Fos immunohistochemistry to map sucrose-cue activated regions. Aim 2 will utilize this mapping information to focus on discrete brain regions to isolate and quantitate dopamine D1 receptor signal cascade proteins, some in basal vs. phosphorylated states, as we have found that D1 receptor antagonism has time-dependent (incubation-dependent) effects on sucrose seeking. Beyond the goal of identifying neural substrates of addiction as a means to informing novel addiction therapies, the studies will be conducted as a means to expose undergraduate researchers to the scientific process. Engaging the students in this way will enhance their training experiences and the research environment at Western Washington University. PUBLIC HEALTH RELEVANCE: Relapse to drug or food seeking presents a significant public health concern as excessive preoccupation with, and consumption of, drugs and food contribute to numerous negative health outcomes. The proposed studies aim to identify differential gene expression in the brains of rats related to relapse behavior with or without the relapse-attenuating pre-treatment of extended enriched environment living conditions. The results of these studies may lead to a better understanding of the molecular biology of relapse behavior and thus facilitate development of novel relapse treatment approaches.