Behavioral Core

行为核心

基本信息

批准号：
10380648
负责人：
Elizabeth J Glover
金额：
$ 21.59万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10380648
关键词：
Abstinence Acute Address Affect Alcohol consumption Alcohol withdrawal syndrome Alcohols Amygdaloid structure Animal Model Anxiety Attenuated Automobile Driving Behavior Behavioral Brain Brain region Chronic Cognition DNA Methylation Data Dependence Development Diet Epigenetic Process Ethanol Experimental Designs Funding Future Gene Expression Genes Glucocorticoid Receptor HDAC2 gene Hippocampus (Brain)Histone Deacetylase Inhibitor Hour Intake Link Liquid substance Measures Medial Mental Depression Modification Motivation Negative Reinforcements Neuroimmune Neurons Phenotype Play Prefrontal Cortex Process Production Protein Isoforms Rattus Recovery Research Personnel Research Project Grants Resources Rodent Role Self Administration Signal Transduction Site Standardization Symptoms Testing Tissues Treatment Factor Validation Ventral Tegmental Area Vorinostat Withdrawal Withdrawal Symptom Work addiction alcohol exposure alcohol research alcohol use disorder brain tissue cognitive control disorder later incidence prevention drinking drinking behavior epigenetic regulation experimental study gamma-Aminobutyric Acid genome analysis histone deacetylase 2 histone modification human model maladaptive behavior negative affect neural circuit neuroadaptation neurotransmission new therapeutic target pre-clinical receptor expression synaptic function whole genome willingness

项目摘要

PROJECT SUMMARY Acute withdrawal from chronic alcohol exposure is associated with a number of symptoms including neuronal hyperexcitability, heightened irritability, and a negative affective state. In addition, acute withdrawal is associated with escalated and uncontrolled alcohol consumption, which is thought to occur, at least in part, due to negative reinforcement as drinking alleviates withdrawal symptoms. The brain undergoes significant neuroadaptations during withdrawal from chronic alcohol exposure. These neuroadaptive processes are thought to play an important role in driving maladaptive behaviors including continued alcohol consumption. During the current funding period CARE investigators have uncovered a number of significant, epigenetically regulated changes in gene expression in the brains of rats withdrawn from chronic ethanol exposure. Interestingly, while some withdrawal-induced epigenetic modifications appear to be common throughout the brain, many are brain region- specific. CARE investigators have further demonstrated that reversal of some of these epigenetic alterations attenuates withdrawal symptoms including those associated with negative affect and altered neurotransmission. However, it is not yet known whether withdrawal-induced epigenetic dysregulation promotes escalated alcohol consumption. The proposed Behavioral Core will allow CARE investigators to address this gap by providing the resources necessary to link withdrawal-induced epigenetic changes with alterations in drinking behavior across all four Research Projects of the CARE. The Behavioral Core will provide CARE investigators with oversight of experimental design, implementation, and analysis of standardized behavioral experiments measuring operant ethanol self-administration in control and ethanol withdrawn rats following either systemic or region-specific reversal of withdrawal-induced epigenetic alterations. The Behavioral Core will also facilitate centralized production of brain tissue from control rats and rats withdrawn from chronic ethanol liquid diet for experiments conducted by the Epigenetics Core. The results generated by the Behavioral Core will allow CARE investigators to establish a causal link between epigenetic modifications and escalated alcohol consumption. Together with findings from each Research Project, these data will inform future work aimed at the development of novel drugs targeting epigenetic factors for the treatment of alcohol use disorders.

项目概要长期接触酒精后的急性戒断与许多症状有关，包括神经元症状过度兴奋、易怒和消极情绪状态。此外，急性戒断也与随着酒精消费的增加和不受控制，人们认为这种情况的发生，至少部分是由于负面影响饮酒可以缓解戒断症状，从而起到强化作用。大脑经历显着的神经适应从长期饮酒戒断期间。这些神经适应性过程被认为发挥着在导致适应不良行为（包括持续饮酒）中发挥重要作用。当前期间 CARE 资助期间的研究人员发现了许多显着的、表观遗传调控的变化从长期乙醇暴露中撤出的大鼠大脑中的基因表达。有趣的是，虽然有些戒断引起的表观遗传修饰似乎在整个大脑中都很常见，其中许多是大脑区域 - 具体的。 CARE 研究人员进一步证明，某些表观遗传改变的逆转减轻戒断症状，包括与负面情绪和神经传递改变相关的症状。然而，目前尚不清楚戒断引起的表观遗传失调是否会促进酒精浓度升高消耗。拟议的行为核心将使 CARE 调查人员能够通过提供将戒断引起的表观遗传变化与饮酒行为的改变联系起来所需的资源 CARE 的所有四个研究项目。行为核心将为 CARE 调查人员提供监督测量操作的标准化行为实验的实验设计、实施和分析对照大鼠和乙醇戒断大鼠在全身或区域特异性后自行给药乙醇逆转戒断诱导的表观遗传改变。行为核心还将促进集中化对照大鼠和从长期乙醇液体饮食中撤出的实验用大鼠脑组织的产生由表观遗传学核心进行。行为核心生成的结果将使 CARE 调查人员能够建立表观遗传修饰与饮酒量增加之间的因果关系。连同每个研究项目的发现，这些数据将为未来旨在开发新药的工作提供信息针对表观遗传因素治疗酒精使用障碍。