Incubation of craving: Abstinence and Environmental Enrichment-mediated Molecula

渴望的孵化：禁欲和环境丰富介导的分子

• 批准号: 8097194
• 负责人: JEFFREY W GRIMM
• 金额: $ 38.67万
• 依托单位: WESTERN WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8097194
• 关键词: Abstinence; Aftercare; Animal Model; Attention; Attenuated; Behavior; Body Weight decreased; Brain; Brain region; Clinical; Cocaine; Cocaine Users; Consumption; Cues; Data; Development; Diet; Dopamine; Dopamine D1 Receptor; Drug Addiction; Drug abuse; Drug usage; Eating; Eating Disorders; Elements; Environment; Exposure to; Food; Funding; Gene Expression; Genetic Transcription; Goals; Health; Human; Immediate-Early Genes; Immunohistochemistry; Individual; Institution; Intervention; Lead; Life; Maps; Mediating; Modeling; Molecular; Molecular Biology; Molecular Profiling; Nucleus Accumbens; Obesity; Outcome; Pathway interactions; Patients; Pattern; Pharmaceutical Preparations; Planning Techniques; Population; Process; Proteins; Public Health; Rattus; Receptor Signaling; Recording of previous events; Relapse; Research; Research Design; Research Personnel; Rewards; Role; Self Administration; Signal Transduction; Stimulus; Students; Sucrose; Time; Tissue-Specific Gene Expression; Training; Universities; Washington; Weight; addiction; attenuation; craving; cue reactivity; drug craving; drug relapse; environmental enrichment for laboratory animals; experience; follow-up; food consumption; food craving; improved; insight; interest; neurobehavioral; novel; paired stimuli; programs; protein expression; relating to nervous system; social; transcription factor

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.

描述（由申请人提供）：重新寻求药物和食物是一个重大的公共卫生问题，因为过度关注药物或食物的寻求和服用会导致许多负面的健康结果。该应用程序使用奖励寻求的大鼠模型，旨在识别具有蔗糖自我施用史的大鼠大脑中的基因表达模式，这些大鼠在已知会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。此外，一些老鼠会在丰富的环境中经历禁欲，我们之前已经证明这种操作可以减弱蔗糖寻求的孵化。基因表达将在第一个目标中使用 Fos 免疫组织化学可视化来绘制蔗糖提示激活区域。目标 2 将利用此映射信息来关注离散的大脑区域，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与磷酸化状态，因为我们发现 D1 受体拮抗作用对蔗糖寻找具有时间依赖性（孵化依赖性）效应。除了确定成瘾的神经基质作为一种为新的成瘾疗法提供信息的手段的目标之外，这些研究还将作为一种手段让本科生研究人员接触科学过程。以这种方式吸引学生将增强他们在西华盛顿大学的培训经验和研究环境。 公共卫生相关性：药物或食物的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大鼠大脑中与复发行为相关的差异基因表达，无论是否经过延长的丰富环境生活条件的减毒预处理。这些研究的结果可能有助于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开发。