Incubation of craving: Abstinence and Environmental Enrichment-mediated Molecula

描述（由申请人提供）：药物和食物寻求的复发是一个重大的公共卫生问题，因为过度关注药物或食物寻求和服用会导致许多负面的健康结果。利用大鼠寻求奖励的模型，本应用程序旨在确定在短期或长期戒断条件下具有蔗糖自我给药史的大鼠大脑中的基因表达模式，这些条件分别产生低水平或高水平的寻求奖励（“渴望的孵化”）。此外，一些大鼠在丰富的环境中会经历禁欲，我们之前已经证明了这种操作可以减轻蔗糖寻求的潜伏期。基因表达将在第一个Aim中可视化，使用Fos免疫组织化学来绘制蔗糖cue激活区域。Aim 2将利用这一图谱信息聚焦于离散的大脑区域，以分离和定量多巴胺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受体拮抗剂对蔗糖寻找具有时间依赖性（孵育依赖性）。除了确定成瘾的神经基质作为一种为新型成瘾疗法提供信息的手段之外，这些研究还将作为一种使本科生研究人员接触科学过程的手段进行。以这种方式吸引学生将提高他们的培训经验和西华盛顿大学的研究环境。

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.