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。使用奖励寻求的大鼠模型，本申请旨在鉴定具有蔗糖自我给药史的大鼠脑中的基因表达模式，所述蔗糖自我给药史是在已知分别产生低水平或高水平的奖励寻求（“渴望的孵化”）的短期或长期禁欲条件下进行的。此外，一些大鼠将在丰富的环境中经历禁欲，我们以前已经证明了这种操作可以减弱蔗糖寻求的孵化。在第一个目标中，将使用Fos免疫组织化学对基因表达进行可视化，以绘制蔗糖提示激活区域。目标2将利用这种映射信息集中在离散的大脑区域，以分离和定量多巴胺D1受体信号级联蛋白，一些在基础与磷酸化状态，因为我们已经发现，D1受体拮抗作用具有时间依赖性（孵育依赖性）的蔗糖寻求的影响。除了确定成瘾的神经基质作为告知新成瘾疗法的手段之外，这些研究还将作为使本科研究人员接触科学过程的手段。以这种方式吸引学生将增强他们的培训经验和西华盛顿大学的研究环境。 公共卫生相关性：药物或食物寻求复发是一个重大的公共卫生问题，因为过度关注和消费药物和食物会导致许多负面的健康结果。拟议的研究旨在确定与复发行为相关的大鼠大脑中的差异基因表达，有或没有延长的丰富环境生活条件的复发衰减预处理。这些研究的结果可能会导致更好地了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.