Component 3 - Frontolimbic circuits, dopamine and attentional bias to alcohol c

组件 3 - 额叶回路、多巴胺和对酒精的注意力偏差

基本信息

批准号：
8593208
负责人：
Donita L Robinson
金额：
$ 21.9万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8593208
关键词：
Acute Address Alcohol consumption Alcoholic beverage heavy drinker Alcoholism Alcohols Amino Acids Animal Model Attention Behavior Behavioral Brain Chronic Cues Data Dopamine Dose Double-Blind Method Electrochemistry Ethanol Functional Magnetic Resonance Imaging Goals Heavy Drinking Human Image Individual Learning Link Measurement Measures Mediating Modeling Molecular Monitor Naltrexone Neural Pathways Neurobiology Nucleus Accumbens Opioid Opioid Receptor Pathogenesis Pathology Pharmaceutical Preparations Pharmacology Phenylalanine Placebo Control Prefrontal Cortex Process Rattus Reaction Time Recording of previous events Relapse Reporting Research Rest Rewards Risk Rodent Role Scanning Seeds Severities Stimulus Substance Use Disorder System Testing Therapeutic Translating Tyrosine Ventral Tegmental Area addiction alcohol craving alcohol cue alcohol exposure alcohol response alcohol reward alcohol seeking behavior alcohol use disorder base binge drinking classical conditioning clinically relevant craving design directed attention drinking drug seeking behavior endogenous opioids in vivo innovation mesolimbic system neural circuit neuroimaging new therapeutic target non-alcoholic novel strategies novel therapeutic intervention optogenetics problem drinker programs relating to nervous system response translational study

项目摘要

Attentional bias toward drug-related stimuli is commonly reported in substance use disorders and is positively correlated with craving. By capturing attention and facilitating drug-seeking behavior, alcohol-associated stimuli can promote continued drinking and relapse. The goals of this project are to (1) determine the neuromodulatory role of dopamine in attentional bias to alcohol cues in heavydrinking humans, (2) model early aspects of attentional bias to alcohol cues in rats, and (3) use that animal model to mechanistically probe brain circuits mediating attentional bias, by using pharmacology, electrochemistry, and optogenetics. These goals synergize with the overall aim of the Center to understand alcohol induced pathology in brain circuits that regulate alcohol use. Moreover, this project potentially identifies novel therapeutic targets for alcohol use disorders. The proposed studies test the overall hypothesis that projections from the prefrontal cortex to the mesolimbic system regulate Pavlovianconditioned attentional bias towards alcohol cues in heavy-drinking humans and binge-alcohol-exposed rats. To address this hypothesis, two aims manipulate dopamine function in humans and rats to determine the effects of dopamine on attentional bias to alcohol cues, and a third aim translates human measurements of frontolimbic connectivity to rat studies that activate and inactivate particular neural pathways in order to identify brain circuits mediating attentional bias. Together, these highly innovative studies reveal how chronic alcohol exposure alters appetitive responses to alcohol cues. These translational studies examine pathology in frontolimbic circuits associated with chronic alcohol exposure that manifest In altered attention and response to alcohol-associated stimuli. The combination of human behavior and imaging with rodent measures of behavior, dopamine release and selective manipulation of prefrontal cortical projections provides a mechanistic approach to identify how alcohol cues usurp attention and behavior to perpetuate compulsive alcohol use.

通常报道了对药物相关刺激的注意偏见。疾病，与渴望正相关。通过吸引注意力并促进寻求毒品行为，与酒精相关的刺激可以促进继续饮酒和复发。这个项目的目标要（1）确定多巴胺在注意力提示中的神经调节作用人类，（2）模拟注意力偏见与大鼠酒精提示的早期方面，（3）使用该动物通过使用药理学的机械探测脑电路的机械探测脑电路，电化学和光遗传学。这些目标与中心的总体目标协同作用酒精诱导调节酒精使用的脑回路中的病理。而且，这个项目可能有可能识别用于酒精使用障碍的新型治疗靶标。提出的研究测试了总体假设从前额叶皮层到中唇系统的投影调节了PavlovianConditioned 在繁殖的人类和暴饮暴食的大鼠中，注意酒精提示的注意力偏见。为了解决这一假设，两个目的是操纵人类和大鼠的多巴胺功能，以确定多巴胺对注意力提示的注意偏见的影响，第三个目标转化了人类的测量与大鼠研究激活和灭活特定神经途径的额叶连通性识别介导注意力偏见的脑电路。这些高度创新的研究共同揭示了如何慢性酒精暴露会改变对酒精提示的起伏反应。这些翻译研究检查了病理学在与慢性酒精暴露相关的额骨电路中表现出在注意力改变和对酒精相关刺激的反应。人类行为和成像与啮齿动物的结合行为的度量，多巴胺释放和选择性操纵前额叶皮质投影提供了一种机械方法来确定酒精如何提示关注和行为以使其永久存在强迫性饮酒。